inviting public submissions under subsection 42ZCZK of the Therapeutic Goods Regulations 1990 (the Regulations)

1. Proposed amendments referred by the delegate for scheduling advice for consideration by the AdvisOI)' Committee on Medicines Scheduling (ACMS).

To create a new Schedule 4 entry for cannabidiol for therapeutic use Cannabidiol with conside.-ation of an Appendix D listing

Thank you for the opportunity to make a submission into the enquiry for the amendment o f schedu ling of cannabidiol.

compounding pharmacist who owns and operates a research and development pharmacy in the elcome the

Advisory Committee on Medicines Scheduling (ACMS) acknowledgement of the need for an enquiry

into the rescheduling of Cannabid iol. There are many clinical trials and a mountain of data on the

benefits and safety issues of cannabidiol. I support this rescheduling completely and believe the right direction for giving access to this beneficial and potentially lifesaving medicine.

~ould also like to submit that the rescheduling of cannabidiol by itself is but a small step in the process of providing safe efficacious cannabinoid medications to the thousands of

legitimate patients that could potentially benefit from this therapy under proper medical supervision.

Giving increased access to doctors and patients to the single pure cannabinoid, cannabidiol, would

do little to help. Currently there are no sources of pure cannabidiol available. The purification and

production of this single moiety would lead to cannabidiol being so prohibitively expensive that it

would be out of the reach of most patients. This has already been proved with the pharmaceutica l nasal spray - which is a extract of cannabis sativa containing the active ingredient Nabiximol, is at $500 per month.

On the other hand rescheduling of NABIXIMOLS (botanical extract of Cannabis sativa which includes the following cannabinoids: tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol,

cannabichromene, cannabidiolic acid, tetrahydrocannabinolic acid, tetrahydrocannabivarol, and

cannabidivarol, where tetrahydrocannabinol and cannabidiol (in approximately equal proportions)

comprise not less than 90 per cent of the total , would allow patients access to pharmaceutical grade Medicina l cannabis with known potency, produced in a regulated pharmaceutical environment.

rover 10 years has consistently controlled and regulated a nabiximol

the approved pharmaceutical company

ith the global distribution to over 25 the publicly owned Global pharmaceutical gian

an Health Department licensed Australian division able to import immediately.

as

1)

2)

plies four different standardized products u pervision:

The THC-Ievel of- is constant around 22 %. The CBD­sl%. This product is available as Cannabis Flower variet~

has a THC-Ievel of around 13,5 %. Its CBD-Ievel is less than 1 %. This is available as Cannabis Flowers variety

3) - has a somewhat lower THC-Ievel of appr. 6,3% and a relatively high percentage of

the non-psycho-active Cannabidiol (CBD) appr. 8 %. - is available as Cannabis Flower --granulate.

4)

It is a variety which is c aracterized as an "Indica" . The other three varieties

ins about 14% THC and less than 1% CBD. Characteristic difference between Indica and Sativa strains species can be found in the presence of

odorous ~ds (terpenes) in the plant. For example, a striking amount of myrcene is

found in --It's a compound that is little or not found in the other three species. Of myrcene is known that is has a calming effect. Like is also presented in granular form.

The ongoing maintenance dose of these standardized pharmaceuticals products is only

about 10% of the price per month of the nabiximol sublingual spray to patients.

Thus rescheduling of cannabinoids I feel should include the rescheduling of the already listed

nabiximol containing products under the same conditions already listed.

Distribution once imported into Australia under TGA permit could flow through the same

State Health Department controlled channels as other narcotics and anabolic agents do.

That is the medicines are prescribed under restricted conditions for certain diseases by

specia list oncologists, neurologists and supplied on prescription by the highly regulated

pharmacy networks that already supply all opiate and narcotic medications.

The argument is about delivering properly regulated medications only to those who have

bone f ide medical conditions. The illicit trade and adverse events of recreational use have no

place in this debate. Not only are they irrelevant but only serve to muddy the waters of the legitimate regula tion of potentially lifesaving medications.

November 17, 2014

To whom it may concern on the Advisory Committee on Medicines Schedu ling,

On behalf ld like to submit a public comment rega rdi ng the proposa l t o create a new Schedu le 4 entry for cannabidiol for t herapeut ic use w ith considerat ion of an Appendix D listing.

standardised concent ration of cannabidiol and a regu lated growth process resu lts in constant qua lity and would contribute to the safety of using t his medicat ion. Importing wou ld also implicate an accelerated introduct ion int o the Austra lian market, compared t o for example sett ing up a GAP-compliant grower in Australia.

For efficacy and safety data of med icinal use of Cannabis, r to the database of t he International Association for Cannabinoid Medicines (IACM). This database contains references to over 300 art icles w ith regard t o the efficacy and tolerability of medicinal Cannabis and it s active ingredients. Addi t iona lly, the use of Cannabis for (defined) medica l pu rposes is lega l in multiple countries, including Belgium, Canada, Germany, Israel, the Netherlands, severa l stat es of the USA and more.

the introduction of medicina l Cannabis in Austra lia or-­istributingstandardised medical cannabis i n~the~

Please f ind our contact detai ls in the accompanying email and below.

Date: 16 November 2014

To: medicines.scheduling@tga.gov.au

RE: The proposal to create a new Schedule 4 entry for Cannabidio l for therapeutic use w ith consideration of

an Appendix D listing.

The following is a public com the Out-of-session ACMS meeting, November 2014.

Summarily, it is suggested by-that the amendments for the single compound known as Cannabidiol

is not an effective way to address the much broader issue of the rescheduling of all Cannabinoids. To select

this one compound in isolation for legislative change is to deny the potential of the w hole range of other

compounds, and the opportunity to take advantage of the other cannabinoids and associated elements of the

Cannabis plant- such as terpenes- that have been shown to have great potential in therapeutic applications.

I refer the committee to the fol lowing study: http://alcalc.oxfordjournals.org/content/40/1/2

That article high lights the different receptors site for cannabinoids in the human body, known as CB1 and CB2

receptors. The article further shows that these different receptors are more dominant in different parts of the

body e.g. CB1 receptors are more concentrated in the brain and associated nervous systems.

The article shows that Cannabidio l is more commonly attracted to CB2 receptor sites, and thus, is much less

effective in treating conditions such as epilepsy, autism, Parkinson's, Dementia, seizures etc, as well as

psychiatric illnesses such as anxiety, PTSD Bi-Polar and schizophrenia. To on ly allow the reschedu ling of

Cannabidiol would preclude effective treatments for these condit ions.

It is also show in the article cited above that the complementary compounds in a 'whole plant' extract­

namely terpenes, have a role to play in clearing and priming the CB1 and CB2 receptor sites, vastly improving

the cannabinoid uptake. To exclude such compounds form any rescheduling would also limit the effectiveness

of any medication based solely on Cannabidiol.

The following quote- and attention to the further links embedded therein- is taken from the article at:

is quoted as saying: "Successful CBD-rich treatment regimens have extended the

lives of advanced cancer patients and others suffering from a wide range of diseases. Most remarkable of all is

the dramatic improvement in numerous cases of paediatric epilepsy attributable to CBD-rich oil extracts, which

stop seizures when nothing else is effective. But CBD-rich remedies with little THC don't always work. ­

of epileptic-have found that adding some THC helps with seizure control in many instances. For some

epileptics, THC-dominant strains are more effective than CBD-rich products.

Physicians and patients are finding that different ratios of CBD and THC are optimal for different conditions

and individuals. A CBD-rich strain or product with little THC is not necessarily a superior treatment option

compared to a balanced CBD-rich remedy with an equal amount of CBD and THC. A CBD-rich extract or strain

with little THC might be optimal for treating anxiety and many seizure disorders, whereas pain syndromes,

Page 2

cancers, and neurodegenerative conditions could benefit from an appropriate amount of THC. One size doesn’t fit all with respect to cannabis therapeutics, and neither does one compound or one product or one strain.” There is a broad body of evidence available that clearly shows the interaction and necessity of different compounds in the therapeutic process. To limit the availability to one single compound, in isolation, is a retrograde step. It does nothing to advance the scientific potential of Cannabinoid therapies, and will result in a wasted effort by the TGA when it proves to be of little benefit as an isolated compound, irrespective of the style of preparation, the source or the proposed application.

asserts that the TGA would best serve the expectation of the Australian public, the hopes of the scientific community and the needs of patients by choosing to reschedule all Cannabinoids and associated compounds from the Cannabis plant to a class that makes them easy to obtain, easy to study and easy to use – the current scheduling of such compounds goes against patient interests, severely limits scientific investigation and causes many social problems by the involvement of punitive measures for no apparently sound scientific or evidence based reason(s). It is not irrelevant to mention in this submission that there is a growing body of evidence from around the world, and from many well respected institutions and individuals - including many experts in various fields - that makes the case for the lifting of restrictions on all Cannabis derived compounds. It is only through such rescheduling that the true nature of Cannabinoids can be studied and ascertained more fully – thus leading to a more complete understanding of all the compounds, their relevant applications rates and the suitability for various conditions that have shown much promise both scientifically and anecdotally. Australia faces a health care crisis in the coming years, and increasing costs to the taxpayer. The rescheduling of Cannabis compounds to allow them to be studied more widely, more easily and cheaply, and across a broad spectrum of conditions can help to both alleviate the spiralling costs of 'conventional' or purely 'patented pharmacological' treatments that are currently used or on the horizon. The development of effective treatments will not only result in better outcomes for patients and the taxpayer funded healthcare system, but will result in on-going employment of researchers, growers, processors and such that will provide an additional economic boost to Australia and increased involvement, credibility and participation in the health care sector on a worldwide basis. Rescheduling of only Cannabidiol is against the national interest, and the interests of both patients and medical science. urges the TGA to broaden the scope of its considerations and finding, and reschedule a broader range of Cannabis compounds, and to disregard the corporate or other vested interests, and to also disregard the dogma and untruths surround other Cannabis compounds, (namely THC) that may encourage such a limiting movement on rescheduling only this one single compound. do not know enough about all the cannabinoids and their combinations to limit the efforts of the TGA to distinctly suggest one compound is the only viable one.

17 November 2014 Email: medicines.scheduling tga.gov.au

Medicines Scheduling Secretariat Therapeutic Goods Administration PO Box 100 (MDP122) WODEN ACT 2606

Dear Sir/Madam,

Re: Proposed scheduling of cannabidiol

takes this opportunity to provide a submission to the consultation on the proposed amendment to the poisons standard for:

Cannabidiol – to create a new Schedule 4 entry for cannabidiol for therapeutic use with consideration of an Appendix D listing.

Cannabis has been the most commonly used illegal drug in Australia. The main active ingredient of cannabis is delta-9-tetrahydrocannabinol (THC) however the plant (Cannabis sativa) consists of many (around 500) natural components including up to around 80 cannabinoids. THC is the major psychoactive ingredient of cannabis while cannabidiol is the major non-psychoactive ingredient.

In Australia, there has been recent and ongoing public debate on the possibility of legalising cannabis for medical purposes. Several jurisdictions are progressing legislative amendments to enable the conduct of trials. This will assist the feasibility of such therapy and recommended parameters around appropriate use to be determined given the evidence base around controlled medical use is still lacking.

Regarding scheduling in Australia, understands the following:

Cannabis (including many different cannabinoids) and synthetic cannabinomimetics are Schedule 9 substances under the Poisons Standard 2014.

Cannabidiol is captured under the Schedule 9 entry for cannabis or under Schedule 8 as a component of nabiximols (botanical extract of C. sativa).

Similar substances included in Schedule 8 are dronabinol (synthetic THC) and nabilone (an analogue of synthetic THC).

Additional controls on possession or supply apply to nabiximols and dronabinol as outlined under Appendix D of the poisons standard.

is aware that in several countries cannabidiol has been granted orphan drug designation for specific symptoms or diseases and/or approval for use in controlled trials to investigate its effectiveness. of cannabidiol being used as an investigational drug.

Although cannabis-related substances are currently included in Schedule 8 or Schedule 9, believes it is appropriate to include cannabidiol as a specific substance in Schedule 4 when it is the sole active ingredient in a therapeutic product. This is based on reasons including the following:

Although a component of cannabis, the effects of cannabidiol are regarded as non-psychoactive and therefore it does not warrant the Schedule 8 classification that applies to nabiximols which is a mixture of cannabidiol and THC (which possesses psychoactive properties).

Cannabidiol is not reported to possess any significant abuse potential.

If the cannabidiol is derived from a botanical source and hence contains other cannabinoids, any permitted levels of non-cannabidiol substances can be specified.

A Schedule 4 entry will ensure appropriate medical supervision.

In addition, the listing of cannabidiol in Appendix D is recommended to ensure the involvement of approved medical practitioners and close monitoring of supply and use of cannabidiol.

While the evidence base of the medical use of cannabidiol is not well established, believes that a Schedule 4 entry and Appendix D listing will facilitate the conduct of clinical trials in an appropriate manner including necessary data collection, analysis and evaluation.

Please do not hesitate to contact if anything in this submission requires clarification.

Yours sincerely,

Application to Amend the Poisons Standard

Submitted by

do not sell cannabis or it's extracts to others. extensively studied the published science from around the world on cannabis and each of it's constituent cannabinoids.

peer reviewed studies and many of the peer reviews. studied all that is currently known about the EndoCannabinoid System (ECS) and the roll it plays in achieving homeostasis or good health, both mental and physical.

17 November 2014

Substance Details

Substance: Cannabidiol (CBD)

Current Poisons Schedule:

Cannabidiol (CBD) does not currently appear as a specific entry in Part 4 of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) and should NOT be given a listing.CBD is not a poison. There is no known toxic dose for CBD, but estimations made by those that have studied it place the LD50 of CBD at >40,000:1 No toxic effect on any normal human cell has ever been indicated.

Page 1 of 8

As Cannabidiol is non-toxic to the human body, it's inclusion under the poisons schedule in

any form is arbitrary and perverse.

However as a constituent of cannabis, the substance may, depending on the origin of the

cannabidiol, be captured by the entry for cannabis in Schedule 9. This situation is absurd as many plant groups (eg. Brassicas, Echinacea) have recently been

shown to contain phyto-cannabinoids that mimic the action of CBD on the EndoCannabinoid

System. Would juice extracts of those plants be captured by a listing of CBD in Schedule 4? many would be captured over time as more is learned about the widespread

occurrence of phytocannabinoids, leading to chaos for individuals and corporations alike in

food preparation.

Cannabidiol is also mentioned in the Schedule 8 entry for nabiximols. However, nabiximols

is defined as a mixture of both L19-tetrahydrocannabinol (THC) and cannabidiol (CBD).

Nabiximols should also not be included in Schedule 8 as the 1:1 ratio of THC:CBD mitigates any psychoactive properties brought by the THC making it not prone to abuse or misuse and

therefore not in need of the restrictions found in Schedule 8. It should more rightly appear as

a Complementary medicine. It is not a synthetic pharmaceutical. It is an herbal extract made from 2 different strains of the cannabis plant one high in THC, the other high in CBD. The 2

extracts are blended together to gain a 1:1 ratio of the 2 compounds which form a CB1

agonist-antagonist pair in the same way that the endocannabinoids, Anandamide and 2-AG form a CB1 agonist-antagonist pair and create no abnormal psychoactivity in an healthy

person. The antagonist only acts directly upon the receptor, the antagonist locks into back of

the agonist and down modulates it's activity and makes it last longer.

The 1:1 ratio has also been achieved through breeding to provide highly medically effective extracts that carry few to any unwanted side effects and do not suffer the expense of

Nabiximols which contains

around $500/ ml of active cannabis oil. Even illicit street supply provides around $60.

died from using whole plant cannabis extracts which have been around for a

couple of centuries, even from uncontrolled illicit street supply. This indicates a need for use

under medical supervision to be unnecessary but guidance for administration for inexperienced users by those experienced in the practice would make reasonable sense to

avoid unwanted side effects that can occur with incorrect strain choice.

Cannabidiol may also be a constituent of hemp seed oil. Hemp seed oil is defined as the oil obtained by cold expression from the ripened fruits (seeds) of Cannabis sativa and is exempted from scheduling provided the oil contains 50 mg/kg or less of tetrahydrocannabinol and is labelled with the warning statement: "Not for internal use or Not to be taken". Australia is the only country on earth apart from New Zealand that does not allow human consumption of cannabis foods. There is no logical reason to do so as any psychoactive cannabinoids such as THC are only found in trace amounts in the seed regardless of strain and the presence of CBD within hemp seed precludes the food leading to a psychoactive reaction.

Page 2 of 8

Proposed Poisons Schedule:

Cannabidiol is a component of Cannabis Sativa, a flowering plant that can be used for its fibre, seed oils and for medicinal and recreational purposes.

In its crude plant form, cannabis is listed in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) as Schedule 9, as it is claimed to be a substance that may be abused or misused. One common component of cannabis, Δ9-tetrahydrocannabinol (THC) can alter a person’s mood and generate feelings of elation or euphoria.

Many claims have been made regarding THC “causing” mental illness, especially schizophrenia. THC is a neuroprotectant and antioxidant, it can cause NO harm to the human body. What THC can do is expose an already existing endocannabinoid deficiency (in the form of the CB1 receptor not releasing enough of the endocannabinoid 2-AG when acted upon by an agonist. Even without using Cannabis a person with this deficiency will develop schizophrenia due to not being able to naturally down regulate the action of the body's own version of THC, as someone without the deficiency does. CBD down modulates the agonist or THC) and is therefore a treatment for the deficiency to relieve the symptoms but not something to fix the underlying cause (usually diet coupled with DNA). Whole plant cannabis extract from fertilised female plants containing both THC and CBD can rebuild the receptors and repair the DNA issues that caused the symptoms in the first place.

Cannabidiol can also alter a person's mood, and though it is not viewed as psychoactive in the major journals, personal experience has shown me it can cause anxiety and agitation in those with an existing anandamide deficiency such as those who on the autism spectrum.

The intent of the proposed schedule entry is to “ensure there is a suitable level of medical oversight over the use of pharmaceutical grade cannabidiol based products and reduce the regulatory burden associated with its current classification as a prohibited substance (Schedule 9, extract of cannabis).”

This however falls at the first hurdle because the endocannbinoid system is NOT taught in medical or nursing schools in Australia and doctors therefore have little to no knowledge of this system of lipids that control virtually all other systems in the human body. The declared that the endocannabinoid system is “ not important to health” opposes cannabis based medicines because they do not understand the method of action. The only true experts on cannabis and the endocannabis system in this country are mostly on a disability pension and have been forced to learn about their medicine because the medical profession has refused to learn about the science that has been done around the world. There are now over 30,000 studies and published articles in PubMed alone on this issue and yet claims more studies need to be done to prove safety. Can't they read? Most pharmaceuticals undergo only a handful of studies before release, so why the discrimination against this one non-toxic plant?

Page 3 of 8

Wilful ignorance is not plausible deny-ability and in the case of the medical profession becomes criminal disregard when it means people are dying by being refused access to life sustaining and life saving non-toxic medical herbs.

Implications of proposed rescheduling on hemp seed oil

It may be noted that it is generally the flowering parts and to a lesser extent the leaves and stems of Cannabis sativa that are used for extraction of cannabinoids. The seeds are simply used as a source of polyunsaturated fatty acids and the SUSMP defines ‘hemp seed oil’ as only cold-pressed oil from the seeds of Cannabis sativa plants.

Low THC hemp seed oil can already be sold without restriction provided it is not intended for human internal use and, at least in some jurisdictions, does not contain whole cannabis seeds. There are a number of hemp seed oil products in the marketplace including cosmetics and body oils. If hemp seed foods are allowed for human use as recommended to the current review of the Australian and NewZealand food standards the cannabis seed oil would be trapped under schedule 4. This outcome would means medical supervision would be required to make salad dressing. Absurd.

Practical effects of a Schedule 4 reclassification

As there are no registered medical professionals within Australia with training in the application of cannbinoid medicines or the function of the endocannabinoid system no meaningful “medical oversight” is possible in Australia at present. Therefore the listing of any cannabinoid for use under Schedule 4 is farcical and really just an exercise in the blind leading the blind! CBD without THC is as prone to causing an imbalance in the body as is THC without CBD. The entourage effect that has been shown to occur with balanced multi cannabinoid extracts outstrips the results from individual alkaloids. All the phytocannabinoids found in the cannabis plant have now been shown to have analogues in the endocannabinoid system that the healthy body produces on demand. The unhealthy body does not produce enough endocannabionoids to achieve homeostasis and requires the adjunct of phtyo-cannabinoids in order to achieve it. Cannabis is a source of essential nutrients and should be made readily available to the public.

It is understood that under section 52D(3) of the Therapeutic Goods Act (1989), the Secretary of the Department of Health and Ageing may consider a change to the SUSMP on his or her own initiative, or following an application. While the submission of this application provides for the issue to be considered by the Advisory Committee on Medicines Scheduling (ACMS), we request that an out-of-session meeting for this proposal be put to the ACMS Chair for his consideration (See Regulation 42ZCZB(3)).

The Secretary of the Department of Health and Ageing should of his or her own initiative immediately de-schedule Cannabis Sativa in all it's forms and varieties. Cannabis is a nontoxic herbaceous plant it is NOT a poison. It lists in the botanical guides in the same family as Hops, Cannabaceae. Cannabis has had a

Page 4 of 8

known medicinal use for nearly 5000 years having been listed in early Chinese writings as one of the major medicinal herbs. In all that time there is not a single recorded incident of fatal cannabis poisoning occurring. The W.H.O. has stated that it is impossible to fatally overdose on Cannabis. This is due to the LD50 (the ratio between a medicinally effective dose and the dose that would kill 50% of the population) of cannabis being greater than 1:20000 which is actually an higher LD50 than that of potable water! It's safety for human consumption is on par with lettuce!As Cannabis is non-toxic to the human body it's inclusion under the poisons schedule is arbitrary and perverse. Cannabis MUST be de-scheduled immediately. The reasons for this are simple.Cannabis is not a poison, so it should not list as a poison.Cannabis is not a narcotic, it does not act on the opiate receptors in the brain stem, it does not suppress the central nervous system, so it should not list as a narcotic.Cannabis is not a drug of dependence, It does not cause a physical addiction, so it should not list as a drug of dependence.

Cannabis should fall under the Agriculture Department for commercial supply of it's fibre and seed and raw ingredients for medical use to suitably equipped industrial facilities. Food safety standards should be imposed through out the processing of all cannabis in order to prevent contamination of the medicinal and food parts of the plant.

Same rules as grapes. Simple.You can grow as many grapes as you want, no licence; You can make as many of those grapes into wine as you want, no licence;You can consume that wine and share it with your friends, no licence;But the moment you wish to sell that wine for public consumption you must get a licence and prove it is meets food safety standards.Same rules should apply to Cannabis. A simple model that works well and with which the community is highly familiar.Commercial distribution of the flowers and the many “medibles” that provide non smoked modes of administration would occur from licensed premises (which would NOT be allowed to distribute alcohol).

Detailed claims against Therapeutic Goods Act 1989, Section 52E

1. Risks and benefits of the use of a substance

Small unblinded trials and other widespread experimental use in humans suggest that cannabidiol has an adverse effect profile that is within the acceptable limits for a Complimentary Medicine and the release of cannabis foods in Australia for human consumption should occur as a matter of urgency.

Given that cannabidiol is not psychoactive and is a separate and distinct cannabinoid entity found in Cannabis, it does not pose the health risks commensurate with a Schedule 9 classification.

Page 5 of 8

2. The purposes for which a substance is to be used and the extent of use of a substance

The risk/benefit profile has been well established. Most cannabis plants contain cannabidiol and there were over 200 Million daily users of cannabis last year according to WHO statistics. Further more as stated in the governments submission Cannabidiol is found in hempseed and over 1 billion people worldwide consumed hemp seed last year without incident. There have been NO adverse effects reported that would fit the profile of having been caused by CBD and many epileptics have reported using cannabis to relieve their symptoms with out any reporting of adverse interactions with other medications. The risk profile is therefore shown to be almost non existent. The wide spread use of cannabis medicines in places like California many of which contain CBD, over the last couple of decades have not lead to any deaths due to toxicity and has not increased the burden of mental health on the community.

3. The toxicity of a substance

CBD is not a poison. There is no known toxic dose for CBD, but estimations made by those that have studied it place the LD50 of CBD at >40,000:1 No toxic effect on any normal human cell has ever been indicated. As Cannabidiol is non-toxic to the human body, it's inclusion under the poisons schedule in any form is arbitrary and perverse.

4. The dosage, formulation, labelling, packaging and presentation of a substance

Irrelevant when the substance is not on the schedule and should not be listed on the schedule.

5. The potential for abuse of a substance

Although cannabidiol is a phytocannabinoid and occurs naturally in Cannabis sativa plants, there is strong evidence that this specific chemical compound is not responsible for the psychoactive effects of cannabis.10 Cannabidiol has very low affinity for both CB1 and CB2 receptors and this is thought to explain its lack of psychotropic activity.10

There is evidence from animal models and early clinical signals that cannabis may actually reduce drug seeking behaviour and normalise drug-induced neuronal abnormalities. Databases of clinical trials show a number of clinical trials that are either ongoing or nearing completion which are researching the use of cannabidiol and Nabiximols as therapeutic agents for people who are opiate dependent, or who are undergoing alleged cannabis withdrawal (which in actual fact is usually nicotine addiction due to the common practice of

Page 6 of 8

recreational users to blend cannabis and tobacco for consumption). To date, these trials have not been completed and no conclusive results are available.

The principle being applied in attempting to treat a theoretical cannabis addiction with whole plant cannabis extract (Nabiximols) is akin to treating alcohol addiction with double malt scotch. Of course it will work. It is the same substance! However the ability of cannabis to mitigate the withdrawal symptoms of many narcotics is widely known throughout the “drug underculture” even if it is not by .

Cannabis does not cause a physical addiction and produces no withdrawal symptom profile of any type. The contaminants that street cannabis may contain due to the lack of quality assurance practiced by criminal consortia can carry physical addiction in users but that is due to the current practice of allowing production and distribution to be handled by criminal who care nothing for the safety of their customers. It is not caused by the cannabis itself.

Australia as a signatory to the United Nations (UN) International Drug Control Conventions, can notify the UNODC of a reservation for the availability of Cannabis and allow it's use 6 months later without offending against the treaty, The UN Single Convention on Narcotic Drugs (1961) and the UN Convention on Psychotropic Substances (1971) both recognise that the medical use of narcotic and psychotropic drugs continue to be indispensable for the relief of pain and suffering, and that adequate provision MUST be made for medical and scientific purposes. The conventions require signatories to observe restrictions about importation and manufacture of narcotic and psychotropic drugs, and to provide estimates ahead of time on the quantities and types of drugs that will be used in medical and scientific research, among other things.

Australia has completely failed to meet this obligation refusing to allow cannabis use in any medical or scientific purpose until very recently and still restricts the availability far beyond what the science dictates is reasonable. Denial of the efficacy and safety of cannabis medicines does not change the scientific facts that have been discovered on the subject by scientists from around the world.

Cannabis, cannabis resin and extracts and tinctures of cannabis are classified as Schedule I drugs, and the UN Convention controls are mandatory whether a Schedule I drug is natural or synthetic.

Schedule 1 drugs are substances that have no known medical usage. Cannabis is not such a substance and therefore must be removed from schedule 1 immediately. The medical uses and effectiveness of cannabis are widely documented and therefore the inclusion of cannabis in schedule 1 is arbitrary and perverse.

The National Coordinating Committee on Therapeutic Goods (NCCTG) Scheduling Policy Framework recommends that any substance, which has therapeutic value and which is included in Schedule I or II of the UN Single Convention on Narcotic Drugs 1961 or in

Page 7 of 8

Schedule II or III of the UN Convention on Psychotropic Substances 1971, be included in Schedule 8.

Cannabidiol would be captured by the definition of cannabis, in particular the inclusion of ‘extracts of cannabis’ in Schedule I of the UN Single Convention on Narcotic Drugs 1961.

This shows the absurdity of the listing of cannabis in Schedule 1 and therefore the reason that a scientific body such as the TGA should immediately de-schedule cannabis from the poisons list and instead list it as a complimentary medicine. It is not a toxic pharmaceutical it is a non toxic herbaceous plant that provides essential nutritional compounds that bring about homeostasis. It is not a narcotic and should not list as a narcotic. It is a food and should be treated as grapevines, which can be used to provide a toxic substance, that is widely used by the public. Cannabis does not have that risk.

6. Any other matters necessary to protect public health

Nil.

Conclusion

Cannabidiol does not meet the NCCTG Scheduling Policy Framework criteria for inclusion as a new entry in Schedule 4 of the SUSMP. In particular, the fact that no medical professional has any training in Australia on the endocannbinoid system or application of cannabinoid medicines precludes them giving any meaningful supervision. The propensity with which cannabidiol may produce dependency is non existent, No report of addiction to CBD has ever been noted in any published article. Suggestion that it may show addictive properties is absurd as it does not directly interface with the pleasure centres of the brain.

Therefore there is no need for medical supervision of the use of CBD which can easily be sourced through consumption of food grade hemp seed.

Page 8 of 8

writing to make comment on the call for public opinion on the proposal "under 42ZCZK of the Therapeutic Goods Regulations 1990 (the Regulations) in

response to the proposed amendment to change the current Poisons Standard to create a new Schedule 4 entry for cannabidiol (CBD)for therapeutic use with consideration of an Appendix D listing. "

this is the best thing to at pomt m tnne. more proven and has the ability to u·eat

many illnesses at once, allowing patients to reduce the overall number of dmgs they need to take. The practice of over prescribing is a growing concem and contributes to eating up health budget.

various altemative herbal medicines - found Cannabis oils and tinctures % ofTHC and CBD

IS no t OXIC

.... ,u ... care; and be able -. - ···---J of life. l do not want to

penmsswn to use imitation cannabis.

To schedule cbd at all is unnecessary. Cannabis should be classified .,u,~uc:u.

- able to be grow and process it to other plants anti

without fear of prosecution.

Anyone wanting to sell cormnercially, should be held to similar standards and licencing as in the wine industry.

There are valid reasons why the public want to legalise the use of cannabis. NOT because­want to get stoned.

This attitude exists because of the lack of acceptance of existing research, u·ials, stigma, and ignorance stermning from lack of education, needs to be addressed so the best decision can be made.

There are many conditions that can be helped only by whole plant extracts and to leave these people on the shelf is not fair and neither is it necessary. CDB will not get people high, so this step will achieve nothing of value – this product can be purchased on line already from any number of websites.

I thank you for the chance to add to this debate.

Below are some links that are relevant

Date: 17 November, 2014. This submission is made under subsection 42ZCZK of the Therapeutic Goods Regulations 1990 (the Regulations) in response to the proposed amendment to change the current Poisons Standard to create a new Schedule 4 entry for cannabidiol [‘’CBD’’] for therapeutic use with consideration of an Appendix D listing. ______________________________________________________________ refer to the above matter and advise, that strongly oppose the current

proposed amendment and make the following submissions. 1. CANNABIS: CURRENT STATUS 1.1 The continuing determination of the TGA, schedules the whole natural botanical cannabis plant, as a ’poison’’. As such, it is deemed an illegal and or prohibited substance, for the purposes of state and federal legislation. 1.2. Notwithstanding this, Nabiximols a pharmaceutically derived cannabis product containing, CBD, THC, terpenes and other substances derived from the Cannabis Sativa plant (‘’cannabis’) (produced is available and authorized for use by the Therapeutic Goods Administration (“TGA”) in Australia, albeit in very limited circumstances. This product however, is I understand, largely inaccessible to many of those who qualify for its use. 1.3. Current scientific and historical data demonstrate, that on the balance of probabilities, that the current inclusion of the natural botanical cannabis sativa plant or ‘’cannabis’’ in the Poisons Standard, is incorrect. 1.4. Whole natural botanical cannabis has scientifically acknowledged medical utility and a number of parliamentary and other international scientific enquiries of note, have advocated its medicinal use. The authorization of products such as Nabiximol by the TGA for limited use, gives further credence to the suggestion, that the current listing for cannabis as a ‘’poison’’ in the Poison Schedule is incorrect. 1.5. It is submitted that in light of the matters referred to above, that a continuing failure to remove cannabis from the current Poison Schedule may be conduct that is viewed as having the potential to mislead and or deceive,

2

the Austral ian publ ic.

1.6. The cannabis plant is noted to contain more than 60 unique structurally re lated phytocannabinoid chemicals. Cannabadiol or CBD is only one of a number of cannabinoids. Science reports that they are still uncertain as to the use and operation of all cannabinoids in the plant. However, they do believe that they all work together synergistically (referred to as the "entourage effect'). There are other properties in the plant including terpenes, which I understand, operate directly on the endocannabinoid receptors found in the human body, to make them more readily available to the up take and use of cannabinoids, by the human body.

1.7. Without all these properties working together, as well as sciences limited knowledge on the function and extent of the operation of other cannabinoids as isolated compounds and or with CBD, the efficacy and safety of CBD only medications and the proposed amendment (CBD) to the Poisons Schedule, must be questioned.

1.8. Cannabis is not a 'one-cannabinoid-fits-all' medicine. The healing power lies in full-spectrum whole natural plant extractions.

In much the same ways as pharmaceutical products and dosage is tailored to address a patients symptoms and tolerance requirements, the same approach is presently being adopted overseas -using whole natural raw botanical plant cannabis extracts/material. Medical practitioners, medical/compassionate care clinics, working with medical scientists/ laboratories and specialist dispensaries /pharmacies in the USA, are successfully identifying various strains of the cannabis plant with varying levels of cannabinoids, to address a patients specific ailments and needs. What they are using however, is whole natural plant extracts and plant materials.

1.9. Science has demonstrated that whilst CBD or CBD dominant, whole natural botanical plant extracted medicinal preparations have therapeutic use, however it has also shown that such use is limited

Reports coming out of the USA and Australia have also noted the limited efficacy of CBD/CBD dominant whole natural plant extractions and have proven that these have been incapable of the exceptional results recently attribute to it by some media sources.

- research and enquiries on this matter, suggests that these ~es were not using pure CBD extractions, but include THC (at varying levels).

understand that high CBD strains of cannabis are rare. I such strains are found in the USA, and are the result of

opme the USA government (the subject to a USA government patent), with cultivation most likely taking place und~iate licensing arrangements, such as those currently witnessed in- USA.

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In Australia, medicinal cannabis use remains illegal. However a number of desperate Australians have risked legal prosecution to access it to address a number of chronic and life threatening illnesses. There have been a number of these self-medicating users and their success stories have featured in the Australian media in recent months. These success stories have been the direct result of whole natural plant extractions from the cannabis plant (not hemp) which are not CBD extractions but are in fact, THC /THC(a) dominant preparations, whose extraction, preparation, application and dosage applications have avoided psychotropic effects deemed by some to be unpleasant. A large proportion of theses success stories feature children suffering from severe life threatening epilepsy. Medical science established that whole plant cannabis extraction was capable of epilepsy back in the 1940s. Such reported success stories involving epilepsy, are therefore hardly surprising. Increasing reports coming out of the USA, show that the efficacy of dominant CBD preparations, do not work for all c with this medical condition and or, have a limited efficacy period, after which such then require and respond to whole natural cannabis preparations which includes THC. This is clearly one example of the entourage effect at work, and the need for whole natural plant medicine. Removing CBD only (as opposed to the entire plant from the Poison Schedule) will mean that some children with this condition will be denied medication, and will undoubtedly die as a consequence. 1.10. Consequently, given the limited efficacy of CBD extractions and or CBD only pharmaceuticals (as opposed to whole natural plant extractions that contain all the properties of the cannabis plant, persons affected by: (a) conditions that are not responsive to CBD or high CBD low THC extractions, (b) Iatrogenic disorders caused by side-effects of a treatment; ( (c) drug interactions; (d) multiple complicating illnesses resulting in contraindications which deny them drug and or other treatment options (e) chemical sensitivities (f) rare and or orphan illnesses will be disadvantaged by the current proposed amendment. Many Australians fit one or more of these categories. 1.11. If the true nature of current parliamentary enquiries is to enable the chronically ill to access medicinal cannabis, then all such patients must be given access to whole natural plant botanical extractions containing all of its

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medicinal properties. CBD or CBD dominant extractions alone, will not meet the state parl iamentary intentions or the current will of the Australian people who have clearly indicated in a number of Australian wide polls, that they want access to whole natural plant cannabis and its extractions, for medicinal use.

1.12. Cannabis is a herbal botanical. Many patients use herbal medicinal products and have been forced to do so because chemically derived pharmaceuticals have been:

(a) harmful (b) ineffective ( (c) unavailable to address their pain, symptoms and suffering (d) are contraindicated due to associated medical conditions/treatments or (e) are financially out of reach of the ordinary consumer.

Consequently, many Australians are unlikely, unwilling and or unable to try anything other than the whole natural botanical plants and or their extractions, grown under scrutinized conditions. Pharmaceutical derived cannabinoid CBD substances will not be a suitable option to many of these Austral ians.

1.13. Mental illness is no longer a valid or justifiable reason to keep natural whole plant botanical cannabis medicine from the people. Studies on cannabis and psychosis suggest an "association" only. There are no studies, that demonstrate "causation" I understand that the cause of psychosis/mental illness, in ana of itself, remains to be determined by medical science. Original studies suggesting an 'association between mental illness and the cannabinoid THC, have proven to be flawed . These studies failed to

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exclude those who had been using cannabis for some time, prior to the study and who may have had pre existing undiagnosed mental illnesses and had been successfully, albeit unknowingly, self medicating using cannabis. I also understand that many of the studies on THC and psychosis were undertaken with street grade cannabis, which is often laced with other chemicals to add to the psychotropic experience of its uses. Such studies cannot be relied on to support an ‘’association’’ of any kind between cannabis and the health of the human consumer, let alone psychosis and or mental health issues, because of the presence of such chemicals. In fact, THC attenuated by high CBD and other properties in the whole plant are now being promoted to treat psychosis and mental illness. Overseas, whole plant natural extractions and plant materials are being used in hospitals and generally in compassionate care medical centers and pharmacies. Undesirable effects from THC in these settings is being attenuated in exactly the same manner commercial pharmaceuticals and other complimentary medicines are: via appropriate preparation, application (i.e. ingesting it raw as juice or vegetable matter; as an oil, tincture or resin; vaporizing; topically as ointment -even via suppository) and dosage. Whilst science has shown that smoking delivers THC more quickly into the system than some other methods (with the possible exception of suppositories), my research amongst medicinal users suggests it is not the medicine of first choice. When it is required, it is not mixed with tobacco. Science has shown, that the risk of increased lung disease is largely due to the presence of tobacco, not cannabis. Suggestions of cannabis being a ‘’gate way drug’’, increasing the risk of road carnage and or increased use amongst the young, have been disproven by current international evidenced-based research in USA states that have legalized cannabis for both medicinal and or recreational use. Every pharmacological product approved by the TGA has risks. A brief review of attests to the fact that such products and their side effect profile, demonstrate that many current pharmaceuticals on the market, are far more dangerous to human health than medical science and historic data show cannabis to be. In fact I submit, that alcohol poses more risks to human health and society, than natural whole plant botanical cannabis extracts and plant matter. And yet, alcohol is readily available and may be manufactured at home. Alcohol is also used for self-medicating purposes –even under the guise of recreational use, in much the same way cannabis today is used in Australia. I personally believe the dichotomy between medicinal and recreational use is false. Science shows, all use benefits the endocannabinoid system in the human body and is therefore, medicinal. Many recreational users report feeling relaxed, calmer, less stressed and anxious – all suggestive that they are reaping medicinal benefits. the scientific evidence shows that the therapeutic benefits of cannabis far outweigh the perceived harm to public health and safety. 1.14.The consequential losses resulting from the continuing determination of cannabis’ listing as a scheduled poison and a prohibited or illegal substance are currently being witnessed in: (a) the deterioration in the health and death of hundreds of thousands of Australians who’s endocannabinoid system would otherwise benefit from

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access to the natural whole botanical plant;

(b) an increase in the general and financial burden to the health care system due to continuing prohibition

(c) the loss of economic opportunities and benefits associated with its cultivation and use;

(d) fear and stress of individuals being unnecessarily forced into a position of breaking the law in order to attend to their/another's health needs currently not being met by the existing health care system

(e) the removal and or threatened removal of chi ldren from the homes of those attending to (d);

(f) the wrongful detention and incarceration and resultant losses associated with the same, of Austral ians who faced with the circumstances at (d) choose to use and or cultivate this plant for their own personal use and or the use of others.

1.15. An amendment of the nature proposed for CBD listing without a complete removal of cannabis from the Poison Schedule, has the potential to:

(a) deny effective treatment to those seeking the entourage effect offered by natural whole plant botanical cannabis extracUplant matter,

(b) will mislead the Australian public on the extent of the efficacy of CBD extractions (independent of whole natural plant extractions or cannabis plant matter);

(c) discriminate against and leave without rel ief, all those Australians who would benefit from the entourage effect of natural whole plant botanical cannabis extracUplant matter

(d) continue and exasperate losses referred to at paragraph 14 above;

(e) halt the forward progression of natural whole plant botanical cannabinoid medicine for many years;

(f) be seen in the views of reasonable minded Austral ians as a poor half measure and as such, an unnecessary, wasteful exercise of tax payer dollars, resulting in further discrimination, suffering and losses.

l do not bel ieve this proposal is in the best interests of Australia~ it may indeed be harmful and or continue to perpetuate the harm---­identified.

2. CBD & HEMP

2.1.Ciosely associated to the cannabis plant is the hemp plant.

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2.2. This plant is distinguished from the cannabis plant on the basis of its low THC but high CBD cannabinoids. 2.3. At present no hemp product is “legal” to consume in Australia, the only country in the world to continue to make this determination despite recommendations to the contrary by the Food Safety Standard Committee. Given this, the current proposed amendment regarding CBD rescheduling comes as a surprise.. 2.4.Science appears to acknowledge CBD as non-psychotropic and in fact, attenuates the psychotropic effect of THC. 2.5. CBD hemp products are aggressively marketed overseas as ‘’dietary supplements’’. believe that this is their rightful classification and that it is not necessary or appropriate to move CBD cannabinoid products to a Schedule 4 prescription item or SUSMP. To do so, would create uncertainty regarding the current status of hemp products, currently illegal to consume in Australia. 2.6. There is some suggestion by those within the hemp industry that this proposed amendment will enable suppliers of existing products (here and overseas) to grow and advertise such as suitable for human consumption. If this is correct, the question arises whether such products will retain their current ‘’over the counter’’ status or require a prescription? Should the legal effect be the later, this outcome would most likely be met by strong objection both from consumers, as well as the hemp industry itself. 2.7. Should this amendment free up the hemp industry to grow and promote products for legal human consumption in Australia, Australians who wish to consume such products (and who have wished to do so for some time) will undoubtedly share the following concerns : (a) quality controls concerning supply of hemp (b) labeling, marketing and associated practices

the hemp plant is a chelator of heavy metals and removes toxins from the soil. As such, Australians such as myself, who would be interested in consuming hemp products for its benefits strictly as a food supplement, would require assurances that soils and growing conditions are free from metals, chemical and toxins that would otherwise be present in the plant. Likewise, sourcing of seed and or plant stock, and other quality control measures are also likely to be a concern for Australian consumers for similar reasons. 2.8. in favor of supporting Australian farming industry and choose products grown under Australian conditions and in accordance with Australian standards and regulations, as opposed to imported products where such conditions are not readily ascertainable. concerned that the current

8

amendment will enable hemp CBD oil derived from plant material grown or sourced overseas, to flood the Australian market and endanger the health and safety of Australian consumers. 2.9. aware of a current practice (predominantly by overseas suppliers here in Australia), of promoting hemp CBD oil to the ill. These suppliers are targeting desperately ill Australians who mistakenly believe that they can acquire (illegally) high CBD/low THC medicinal cannabis oil/products here in Australia and that the hemp oil being promoted is the same as medicinal extracts and preparations from the cannabis plant. I understand that prices for small quantities of this oil are being sold for hundreds of dollars, which you would expect to pay for a pharmaceutical grade product. As there is no quality control regulating soil quality or the sourcing of seed or seedlings, very ill Australians could be consuming an end product riddled with heavy metals and other toxins pulled by the plant from contaminated soils. It is hardly surprising therefore, to read overseas reports of people becoming very ill after consuming these products.

believe the proposed amendment may see an escalation in such poor, unjustifiably expensive products and confusing advertising claims. 2.10. It has been suggested by the in its submissions on this subject that‘ ’definitive and specific scheduling of cannabidiol will ensure regulatory certainty for those conducting clinical trials with this substance.’’

the only certainty provided to those in conducting clinical trials involving any CBD is to remove cannabis from the poison schedule entirely. CBD after all, if not extracted from Hemp (a dietary supplement and not a synergistic plant medicinally) will require extraction from a currently scheduled poison and listed prohibited substance. This would create obvious problems for cultivators, product manufacturers and scientific researchers alike.

therefore, that to move forward with the current proposed amendment: (a) may create confusion around the status of hemp products; (b) create an unnecessary regulatory regime for an over counter hemp product (food supplement) deeming the need for a prescription and therefore creating an unreasonable expense to the tax payer; (c) has the potential (without regulation into quality control and product standards) to introduce hemp products which harm the health of the public, which in turn: (d) may lead to increased costs and associated set backs for the potentially Australian lucrative hemp industry

9

(e) has the potential to mislead Australian consumers on the nature of competing CBD based products in the market place (hemp –v- medicinal cannabis) and take advantage of this by charging unreasonable pharmaceutical grade prices without attendant scrutiny that is associated with pharmaceutical grade products; (f) will not create regulatory certainty for clinical trials involving CBD, but may, without removing cannabis completely from the poison schedule, leave them vulnerable to prosecution for cultivation and or possessing a prohibited substance. 3. Cannabis – Complementary Medicine Classification propose that the TGA give consideration to re scheduling cannabis and

removing it completely from the Poisons schedule for the reasons aforementioned. 3.1.The cannabis plant is a botanical substance. As such, believe it would be more appropriately re classified as a botanical ingredient and given a complimentary medicine category listing 3,2.This would overcome many of the problems and failings of the current proposed amendment I have outlined. 3.3. It would also: (a) make the plant immediately accessible to health and allied health professionals, patients and medical researchers (b) allow for the establishment of the overseas model of compassionate clinics and medical dispensaries/pharmacies, supervised by a doctors and associated allied health personnel who would oversee a patients use and progress, and record results which would also be beneficial for further scientific research. This would ease the present burden for Australian medical practitioners having to abandon patients who have no recourse to standard medical products and services, for fears of prosecution by the law and or de registration by medical boards. Such clinics in the USA, work in tandem with local cannabis farmers, horticulturalists, scientists and laboratories, who grow, manufacture and test, the most appropriate variety of cannabis plant and product, for individual consumption and ailments. (c) make access to cannabis' medicinal properties less complicated and costly – in terms of time, human suffering and creating unnecessary further regulatory complication; (d) bring Australia into line with USA and many other countries currently or currently working towards instigating this model;

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(e) reflect popular consensus amongst the Australian people who want to see this take place and which is being increasingly reflected in recent judicial determinations of those who have been prosecuted in recent times for cultivation and or possession for medicinal purposes.

the Secretary of the Commonwealth Department of Health, has the power to amend and initiate such a change in the Poisons Standard under the Scheduling Policy Framework for Medicines and Chemicals, on his or her own initiative pursuant to S52D(3) of the Act. . Closing Remarks Current science and historical data promoting the use of whole natural botanical cannabis plant extraction/material as safe and having medicinal value; limitations on the efficacy and reach of CBD extractions to aid those seeking the entourage effect offered by natural whole botanical cannabis plant extractions/plant matter; the inconsistency of the proposed amendment with the intention of state parliaments to assist and give access to all members of the Australian public seeking medicinal cannabis (ie: whole natural botanical cannabis plant extractions/material) in chronic and terminal conditions; social consensus/the overwhelming majority of Australian people calling for access to whole natural botanical cannabis plant extracts/material for medicinal use; successful overseas use of whole natural botanical plant cannabis extracts and plant matter within compassionate care clinics, pharmacy models and ancillary quality control services; confusion and increased costs in the hemp industry and associated risks to public health from consuming questionable hemp products; barriers to further medical research and economic development; burdening costs of health care with an increasing ageing population; as well as the current potential legal liability and increasing identified losses, which the government / TGA may continue to be exposed to for retaining the current scheduling of cannabis -are, all compelling reasons to forego the current proposed amendment and rather, re assign cannabis to its appropriate place within a complimentary medicine classification.

wish to take this opportunity to thank you for the opportunity to contribute to this important issue. Yours Sincerely

Advisory Committee for Medicines Scheduling

Out of Session Meeting, November 2014

Comments by to the proposed amendments referred by the delegate for

scheduling advice

Cannabidiol

17 November 2014

Page 2 of 3

Introduction

welcomes the opportunity to comment on

proposed amendments to the Standard for the Uniform Scheduling of Medicines and

poisons (SUSMP) being considered by the Advisory Committee on Medicines Scheduling

(ACMS) at its out-of-session meeting in November 2014.

Comments on Proposed Amendments

has considered the proposed amendments to the SUSMP of relevance to

community pharmacy, with particular reference to Section 52E(1) of the Therapeutic Goods

Act 1989. We provide comments for the following proposed amendments in line with

the rationale for our position provided below:

1- Cannabidiol- Schedule 4 listing with consideration of Appendix D Listing

Proposal 1 Cannabidiol- Schedule 4 listing with Appendix D

Listing

(Proposal to create a new Schedule 4 entry for cannabidiol for therapeutic use with consideration of an

Appendix D listing)

is supportive of ongoing appropriate investigation into medicines and

treatment that have the potential to improve the quality of life of people, particularly for

living with chronic illness or who are terminally ill.

believes the most appropriate classification for cannabidiol is Schedule 8 with

listing under Appendix D, paragraph 3 which would require a medical practitioner to

obtain authorisation by the Secretary of the Commonwealth Department of Health in

order prescribe this drug to patients. This would be consistent with the scheduling status

of the other cannabis derivatives: drobabinol and nabiximols.

We note that the announced on 16 September 2014 that a Working

Group would be formed to initiate a clinical trial for medical cannabis. The trial would

explore how cannabis could provide relief for patients suffering from debilitating or

ACMS – November 2014

Page 3 of 3

terminal illnesses.1 The will also be taking the lead in an upcoming

cross-jurisdictional trial and this scheduling amendment will enable greater accessibility of

cannabidiol for this purpose. This is particularly important as certain jurisdictions do not

allow access to Schedule 9 substances, even for medical purposes.

Risks and benefits of the use of a substance2

Cannabidiol (CBD), a major non-psychotropic constituent of cannabis, has multiple

pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-

inflammatory properties. However, little is known about its safety and side effect

profile in animals and humans and further studies are required.3 There is also mixed

evidence regarding its efficacy in treating specific conditions.4 5

As a result, believes cannbidiol should be restricted to use in cases where

patients are not responding to treatments and or medicines which have a more

established efficacy and risk profile.

The inclusion of cannabidiol in Schedule 8, is consistent with the listing of similar

substances drobabinol and nabiximols and ensures the dispensing of this medicine is

recorded in a Controlled Drugs register. This will reduce the likelihood of cannabidiol

being misused and abused.

Recommendation

believes cannabidiol should be listed under Schedule 8 as well as listing under Appendix D, paragraph 3. This is consistent with the listing of similar substances drobabinol and nabiximols.

1 2 Section 52E(1A)- Therapeutic Goods Act 1989 3 Machado Bergamaschi, M., Helena Costa Queiroz, R., Waldo Zuardi, A., & Crippa, A. S. (2011). Safety and side effects of cannabidiol, a Cannabis sativa constituent. Current drug safety, 6(4), 237-249. 4 Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in

murine collagen-induced arthritis. Proceedings of the National Academy of Sciences, 97(17), 9561-9566. 5 Consroe, P., Laguna, J., Allender, J., Snider, S., Stern, L., Sandyk, R., ... & Schram, K. (1991). Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacology Biochemistry and Behavior, 40(3), 701-708.

Australian Government Therapeutic Goods Administration

Attention: The Advisory Committee on Medicines Scheduling

Please note: All identifying information including name, address and email is to remain confidential please and not be published

17th November 2014

Dear Sir/Madam,

Re: Invitation for public comment - Out-of-session ACMS meeting, November 2014

Notice inviting public submissions under subsection 42ZCZK of the Therapeutic Goods Regulations 1990 (the Regulations)

Proposed amendments referred by the delegate for scheduling advice for consideration by the Advisory Committee on Medicines Scheduling (ACMS).

Substance Proposal

Cannabidiol: To create a new Schedule 4 entry for cannabidiol for therapeutic use with consideration of an Appendix D listing

In Australia and globally there exists a critical demand for patients requiring cannabinoid medicine for serious medical conditions which otherwise may remain unresolved or intractable even under other significant pharmaceutical protocols. Many countries internationally have produced effective clinical trials and research proving its safety and efficacy in successfully treating many of these conditions.

agree only with the proposed scheduling as an interim measure, this measure is insufficient. This proposed change does not create regulation that recognises the full therapeutic properties of the cannabis plant and whole plant properties essential for treating a significant number of medical conditions.

would like to draw your attention to the fact that in the USA in some states the introduction of just “CBD only” laws came about due to the increasing publicity surrounding intractable epilepsy and seizure disorders especially. Similar to much of the publicity surrounding this plant in Australia and the relative success of Cannabinoids to treat intractable epilepsy and epilepsy syndrome patients.

In some states in the USA this demand has led some lawmakers to consider passing legislation that only allows patients to access marijuana oils that are high in CBD and that have low THC (tetrahydrocannabinol).

Page 1 of 5

Unfortunately this has meant that even some patients with severe cases of Dravet Syndrome in the USA have learned in the most difficult way that some higher amounts of THC (tetrahydrocannabinol) is also critical to their optimum seizure reduction, not the CBD alone.

Whilst it is pleasing that consideration is being given to the option of CBD therapeutic use in Australia, which may provide some relative relief for patients with seizure disorders, unfortunately this still falls well short of what is actually required for the majority of patients requiring this medicine to be available as a medical treatment. Unfortunately any consideration of this Cannabinoid property alone will exclude the vast majority of patients who can potentially benefit from cannabinoid medicine.

Studies have shown that the THC property found within Cannabis can alleviate a host of debilitating or life threatening conditions and their side effects, including:

• Nausea and Loss of Appetite , Body Wasting or Cachexia1

• Pain2

• Multiple Sclerosis3

• Alzheimers4

• Post Traumatic Stress Disorder5

• Specific types of Cancer6, 7, 8, 9, 10, 11

For example the new research12 by specialists at studied the treatment of brain cancer tumours and found that the most effective treatment was to combine active chemical components of the cannabis. Both properties, the tetrahydrocannabinol (THC) and cannabidiol (CBD) were tested as part of the research into brain cancer. Brain Cancer is a disease which is particularly challenging to treat and according to the Australian Cancer Council there are 1400 cases of malignant brain cancer diagnosed in Australia each year and about 1100 people die from the disease each year. It also has a particularly poor prognosis as the rate of survival after five years of patients' diagnosis is around 10%. To have a solution such as this for a disease that’s mostly fatal is a breakthrough which needs to be embraced by Australia. But in order to have this solution Australia must also understand the need for the whole plant extracts and THC.

Further to this it is the research of has proven the synergistic effects of CBD and THC combined particularly in

the treatment of brain and breast cancers:

• Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells13

• Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells14

Research from this study shows:

“The cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonist, Δ9-tetrahydrocannabinol (THC), has been shown to be a broad range inhibitor of cancer in culture and in vivo, and is currently being used in

Page 2 of 5

a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB1 and CB2 receptors, can modulate the actions of Δ9-THC. However, there are conflicting reports as to what extent other cannabinoids can modulate Δ9-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Δ9-THC. We therefore tested cannabidiol (CBD), the second most abundant plant derived cannabiniod, in combination with Δ9-THC. In U251 and SF126 glioblastoma cell lines, Δ9-THC and CBD acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species (ROS) and apoptosis as well as specific modulations of extracellular signal-regulated kinase (ERK) and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of CBD to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients.”

cannabinoid treatment (inclusive of THC and CBD, and whole plant properties) overseas and this has worked so effectively that

had a significant reduction in This could not have been possible without the combination of both THC and CBD as well as other critical properties of the whole plant.

It is hope for the future treatment of patients that Australia can recognize the whole plant properties including THC and its role particularly in fighting cancer and treating many other diseases and symptoms so that many patients can benefit.

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References:

1 Nausea and Loss of Appetite , Body Wasting or Cachexia http://www.ncbi.nlm.nih.gov/pubmed/21175589

2 Pain http://www.ncbi.nlm.nih.gov/pubmed/21426373 and also http://www.ncbi.nlm.nih.gov/pubmed/22880540

3 Multiple Sclerosis Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. http://www.ncbi.nlm.nih.gov/pubmed/24035293

4 Alzheimers http://www.ncbi.nlm.nih.gov/pubmed/17140265?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed ResultsPanel.Pubmed RVDocSum A molecular link between the active component of marijuana and Alzheimer's disease pathology.Eubanks LM, Rogers CJ, Beuscher AE 4th, Koob GF, Olson AJ, Dickerson TJ, Janda KD. Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

5 Post Traumatic Stress Disorder http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12152079&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed ResultsPanel.Pubmed RVDocSum The endogenous cannabinoid system controls extinction of aversive memories. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgänsberger W, Di Marzo V, Lutz B. Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.

6 Specific types of Cancer http://www.ncbi.nlm.nih.gov/ Cannabinoids selectively inhibit proliferation and induce cell death of cultured human glioblastoma multiforme cells. Journal of Neurooncology. 2005 http://www.ncbi.nlm.nih.gov/pubmed/17931597 Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Athanasiou A, Clarke AB, Turner AE, Kumaran NM, Vakilpour S, Smith PA, Bagiokou D, Bradshaw TD, Westwell AD, Fang L, Lobo DN, Constantinescu CS, Calabrese V, Loesch A, Alexander SP, Clothier RH, Kendall DA, Bates TE. School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK http://www.ncbi.nlm.nih.gov/pubmed/16078104 Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. McAllister SD, Chan C, Taft RJ, Luu T, Abood ME, Moore DH, Aldape K, Yount G. California Pacific Medical Center Research Institute, 475 Brannan St., Suite 220, San Francisco, CA 94107, USA mcallis@sutterhealth.org

7 Cannabinoids and Cancer http://www.ncbi.nlm.nih.gov/pubmed/16250836 Natalya M. Kogan

8 Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines http://www.ncbi.nlm.nih.gov/pubmed/14617682 Paola Massi, Angelo Vaccani, Stefania Ceruti, Arianna Colombo, Maria P. Abbracchio, and Daniela Parolaro

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Department of Pharmacology, Chemotherapy and Toxicology (P.M., A.C.), and Department of Pharmacological Sciences, School of Pharmacy, and Center of Excellence for Neurodegenerative Diseases, University of Milan, Milan, Italy (S.C., M.P.A.); and Department of Structural and Functional Biology, Pharmacology Unit and Center of Neuroscience, University of Insubria, Busto Arsizio (Varese), Italy (A.V., D.P.)

9 Cannabinoids for Cancer Treatment http://www.ncbi.nlm.nih.gov/pubmed/18199524 progress and promise. Sarfaraz S, Adhami VM, Syed DN, Afaq F, Mukhtar H. Chemoprevention Program, Paul P. Carbone Comprehensive Cancer Center and Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.

10 Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases http://www.ncbi.nlm.nih.gov/pubmed/18159069 1. Ramer R, Hinz B. Institute of Toxicology and Pharmacology, University of Rostock, Schillingallee 70, Rostock D-18057, Germany

11 A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. http://www.ncbi.nlm.nih.gov/pubmed/16804518 Guzmán M, Duarte MJ, Blázquez C, Ravina J, Rosa MC, Galve-Roperh I, Sánchez C, Velasco G, González-Feria L. Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid 28040, Spain. mgp@bbm1.ucm.es

12 http://www.sgul.ac.uk/media/latest-news/cannabis-extract-can-have-dramatic-effect-on-brain-cancer-says-new-research

13 Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. http://www.ncbi.nlm.nih.gov/pubmed/18025276 McAllister SD, Christian RT, Horowitz MP, Garcia A, Desprez PY. California Pacific Medical Center, Research Institute, 475 Brannan Street, San Francisco, CA 94107, USA. mcallis@cpmcri.org

14 Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. http://www.ncbi.nlm.nih.gov/pubmed/16078104 McAllister SD, Chan C, Taft RJ, Luu T, Abood ME, Moore DH, Aldape K, Yount G. California Pacific Medical Center Research Institute, 475 Brannan St., Suite 220, San Francisco, CA 94107, USA. mcallis@sutterhealth.org

Page 5 of 5

The delegate of the Secretary of the Department of Health

Therapeutic Goods Administration

via medicines.scheduling@tga.gov.au

Dear Sir/Madam

Re: proposed amendments to the current Poisons Standard to create a new Schedule 4

entry for cannabidiol for therapeutic use with consideration of an Appendix D listing

acknowledges that cannabidiol has constituents that have potential therapeutic

uses. support appropriate clinical trials of potentially therapeutic cannabinoid

formulations to determine their safety and efficacy compared to existing medicines, and

whether their long-term use for medical purposes has adverse effects.

is leading a collaborative trial, with the

support of the Commonwealth and other states and territories, to explore how cannabis can

offer relief to patients suffering from a range of debilitating or terminal illnesses. note

that the has formed a Working Group to set up the clinical trial and

consider all relevant issues including the scope of the trial, and the most appropriate way to

advance the availability of safe and effective cannabis derived products. It is not clear to

if the proposal to reschedule cannabidiol from Schedule 8 to Schedule 4 pre-empts the

advice of that working group.

However, as cannabidiol can offset the effects (altered mood and the feeling of a 'high') of

delta-9 tetrahydrocannabinol (THC), considers it may be less likely to be sought

out for recreational purposes. Consequently, there may be no greater risk of abuse of

cannabidiol if it is rescheduled to Schedule 4.

We assume that the proposed Appendix D listing would be the same as currently applies to

the Schedule 8 listing of cannabidiol i.e. Poisons available only from or on the prescription

or order of an authorised medical practitioner.

On balance, supports the proposed rescheduling of cannabidiol to Schedule 4 with

the current Appendix D listing.

Yours faithfully

13 November 2014

E-Mail karger@karger.com

Comment

Pharmacology 2014;93:1–3 DOI: 10.1159/000356512

Cannabis Finds Its Way into Treatment of Crohn’s Disease

Rudolf Schicho   a Martin Storr   b

a   Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz , Austria; b   Department of Medicine II, Klinikum Grosshadern, Ludwig Maximilian University, Munich , Germany

likely include peripheral actions on cannabinoid (CB) re-ceptors 1 and 2 (CB 1 and CB 2 ), and may also include cen-tral actions.

The past 10 years have seen a constant rise in publica-tions dealing with the anti-inflammatory effects of CBs and the potential underlying mechanisms. Preclinical data on the ameliorating effect of synthetic and natural CBs in animal models mimicking features of IBD have been rapidly evolving. The reasonable idea that CBs would also be beneficial in IBD patients was mainly based on results from experiments in CB receptor knockout mice and on data using CB receptor agonists and antago-nists. Following a previous publication of a retrospective, observational study by Naftali et al. [2] and a question-naire performed by a different group in patients with ul-cerative colitis and Crohn’s disease [3] , both revealing symptom relief and improvement after use of cannabis, Naftali et al. [1] have now presented a placebo-controlled prospective study in 21 patients with Crohn’s disease un-responsive to standard IBD treatment. Although the pri-mary end point of induction of remission was statistical-ly not achieved, they were able to demonstrate that an 8-week treatment with tetrahydrocannabinol (THC)-rich cannabis caused a decrease in the Crohn’s disease activity index in 90% of patients without producing sig-nificant side effects. The authors rightfully concluded that a larger patient group is warranted for future studies.

This is the first clinical trial on the effect of cannabis in IBD, and it confirms what has been suggested for a long time from experimental studies, namely that CBs may

Key Words

Inflammatory bowel disease · Cannabinoids · Prospective study

Abstract

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clini-cal study now shows that the medicinal plant Cannabis sa-tiva has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a pro-spective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn’s disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabi-noid receptors 1 and 2, and may also include central actions.

© 2013 S. Karger AG, Basel

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A re-cent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel dis-eases (IBD). In a prospective placebo-controlled study, Naftali et al. [1] have shown what has been largely antici-pated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn’s dis-ease. The mechanisms involved are not yet clear but most

Received: October 18, 2013 Accepted: October 21, 2013 Published online: December 17, 2013

Rudolf Schicho, PhD Medical University of Graz Institute of Experimental and Clinical Pharmacology Universitätsplatz 4, AT–8010 Graz (Austria) E-Mail rudolf.schicho   @   medunigraz.at

© 2013 S. Karger AG, Basel0031–7012/13/0932–0001$38.00/0

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provide anti-inflammatory effects and symptomatic ben-efit in patients with IBD. The physiological basis for the beneficial effects of cannabis has been established a while ago and unraveled since then. The discovery of CB recep-tors and endogenous molecules activating these receptors led to the description of a coordinated network that is in-herent to the mammalian organism, the so-called endo-cannabinoid system. This system consists of the canoni-cal CB receptors (CB 1 , CB 2 ), their endogenous ligands anandamide and 2-arachidonoyl glycerol (2-AG), also called endocannabinoids, and their synthesizing and de-grading enzymes. What capsaicin, the pungent ingredi-ent of chili, is for vanilloid receptors and morphin for opioid receptors is THC, the psychedelic ingredient of cannabis, for CB receptors: the predominant herbal li-gand. Thus, THC mimics the actions of anandamide and 2-AG.

The wall of the gastrointestinal tract houses all compo-nents of the endocannabinoid system. Recent data show that these components are differentially expressed in hu-man IBD indicating a regulatory role in the disease pro-gression [4] . While anandamide and its synthesizing en-zyme display lower levels in ulcerative colitis, expression of CB 2 receptors and enzymes responsible for synthesis and degradation of 2-AG were increased [5] . The findings

indicate that the CB 2 receptor plays a key role in the ame-liorating effect of CBs in IBD. The precise mechanism as to how CBs contribute to the improvement of IBD, how-ever, is not clear but by use of experimental models of intestinal inflammation we are able to define a picture on how and at which targets CBs cause improvement of inflammation.

CB 1 and CB 2 receptors are located at the colonic epi-thelium, and a protective effect of THC via epithelial per-meability is conceivable ( fig. 1 ). Therefore, CBs could en-hance epithelial wound closure in the colon [6] . One of the prominent features of CBs in experimental intestinal inflammation is their effect on immunocytes which main-ly express CB 2 receptors. Upon CB 2 activation, T cells un-dergo apoptosis and decreased proliferation in colitis [7] . Additionally, activation of CB 2 diminishes the recruit-ment of neutrophils, T cells and macrophages to the in-flamed colon [7] . CB receptors are also found in the en-teric nervous system (ENS), which controls gut motility and secretion [8] . CB 1 receptors present in the ENS rep-resent a break that protects the ENS from hyperstimula-tion, a situation easily caused by overexpression of in-flammatory mediators that activate the ENS during IBD. Therefore, activation of CB receptors by THC may reduce hypermotility associated with the inflammation of the gut

Fig. 1. Potential targets and mechanisms of CBs involved in the improvement of IBD. Natural and synthetic CBs act via intestinal CB 1 and CB 2 receptors to regulate epithe-lial permeability, motility, secretion (via the enteric nervous system), as well as leu-kocyte migration, recruitment and apopto-sis. As the site with the highest CB 1 expres-sion (but also some CB 2 expression), the brain may modulate motility, the sensation of pain and unpleasantness, thus positively influencing the inflammatory process.

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Leukocyte recruitmentMigrationApoptosis

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[9] . The reduction of hypermotility may consequently alleviate diarrhea producing beneficial effects for the patient.

It should be emphasized that the brain is the major site of CB 1 expression and that the presence of CB 2 has also been detected in the brainstem [8] . The use of cannabis in improving inflammation could therefore well include central effects, such as a reduction in pain sensation and relief of nausea and feeling of unpleasantness. One report suggests that a full anti-inflammatory response of CBs in gut inflammation includes the central nervous system since a peripherally restricted CB 1 /CB 2 receptor agonist was either not effective or too weak to improve colitis, depending on the experimental model used [10] .

In their prospective study, Naftali et al. [1] used THC-free cannabis as placebo with no other CBs present. How-ever, we should consider that also other ingredients of cannabis, such as cannabidiol, cannabigerol and tetrahy-drocannabivarine, all of them nonpsychotropic compo-nents of cannabis, have proven anti-inflammatory effects in experimental intestinal inflammation [9] . Their ac-tions partly involve non-CB receptor mechanisms via, for instance, peroxisome proliferator-activated receptors

(PPARs) and transient receptor potential cation channels subfamily V receptors (TRPVs) and should be regarded as additive beneficial effects of cannabis in the improve-ment of colitis in addition to THC-mediated effects.

In summary, in agreement with the ancient use of can-nabis in intestinal disturbances and one decade of animal research, cannabis was shown in a clinical trial to reduce symptoms in patients with Crohn’s disease. This elegant translation should be followed by larger trials confirming these results and by trials establishing the involved mech-anisms to open a promising direction for future treat-ment of IBD.

Acknowledgements

R.S. is supported by grants from the Austrian Science Fund (FWF P 22771 and P 25633). M.S. is supported by the Deutsche Forschungsgemeinschaft.

Disclosure Statement

The authors have no conflict of interest to declare.

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