Marijuana: Modern Marijuana: Modern Medical ChimaeraMedical Chimaera

Roland J. LamarineRoland J. Lamarine

Journal of Drug EducationJournal of Drug Education

Vol. 42(1) 1-11, 2012Vol. 42(1) 1-11, 2012

ChimaeraChimaera

Greek mythology: creature with lion’s Greek mythology: creature with lion’s head, goat’s body, & serpent’s tail head, goat’s body, & serpent’s tail capable of vomiting flames.capable of vomiting flames.

Chimerical properties: imaginary, Chimerical properties: imaginary, fanciful, or fantasticfanciful, or fantastic

Cannabinoids as Therapeutic Cannabinoids as Therapeutic ToolsTools

Oscar Prospero-Garcia et al.Oscar Prospero-Garcia et al. Marijuana affects series of brain Marijuana affects series of brain

receptors: CB1R, CB2R, etc.receptors: CB1R, CB2R, etc. What we know so far:What we know so far: EndocannabinoidsEndocannabinoids modulate modulate

behaviors: food intake, sleep-wake behaviors: food intake, sleep-wake cycle, learning & memory, motivation, cycle, learning & memory, motivation, pain perception, motor control, & morepain perception, motor control, & more

Brief HistoryBrief History

1964, Mechoulam discovered THC1964, Mechoulam discovered THC 1988, Howlett receptors in brain (CB1R)1988, Howlett receptors in brain (CB1R) 1992, Devane isolated anandamide in 1992, Devane isolated anandamide in pig’s brain; CB2R discoveredpig’s brain; CB2R discovered 1994, 2-AG in dogs; oleamide in cats1994, 2-AG in dogs; oleamide in cats So far at least 8 endogenous cannabinoids So far at least 8 endogenous cannabinoids

discovered, 8 synthetic cannabinoids, & 4 discovered, 8 synthetic cannabinoids, & 4 therapeutic compounds developedtherapeutic compounds developed

MARIJUANA EFFECTSMARIJUANA EFFECTS

1. 1. HypothlalamusHypothlalamus: increased appetite: increased appetite

2. 2. Brain stemBrain stem: nausea relief; lowered BP;: nausea relief; lowered BP; drowsiness; lowered: pain, spasticity, & tremordrowsiness; lowered: pain, spasticity, & tremor

3. 3. Cerebral cortexCerebral cortex: altered consciousness; perceptual : altered consciousness; perceptual distortions; memory impairment; delusions; distortions; memory impairment; delusions; hallucinationshallucinations

4. 4. HippocampusHippocampus: memory impairment: memory impairment

5. 5. CerebellumCerebellum: loss of coordination: loss of coordination

6. 6. AmygdalaAmygdala: changes in anxiety; panic attacks; lowered : changes in anxiety; panic attacks; lowered

traumatic memories; decreased hostilitytraumatic memories; decreased hostility

Theoretical Uses of Theoretical Uses of CannabinoidsCannabinoids

Facilitation or blockadeFacilitation or blockade Food IntakeFood Intake: increase calories from : increase calories from

sweet snackssweet snacks CB1 antagonism for anorectic effect, CB1 antagonism for anorectic effect,

Rimonabant (depression/anxiety)Rimonabant (depression/anxiety) SleepSleep: cannabis induces drowsiness;: cannabis induces drowsiness; Rimonabant for wakefulness?Rimonabant for wakefulness?

Learning + MemoryLearning + Memory: negative effect on : negative effect on short-term memoryshort-term memory

Extinction of fear memories & Extinction of fear memories & maladaptive behaviors: PTSD, OCD?maladaptive behaviors: PTSD, OCD?

Therapeutic PropertiesTherapeutic Properties:: Inflammation, pain, muscle spasticity, Inflammation, pain, muscle spasticity,

anxiety, depression, fatigue, insomnia, anxiety, depression, fatigue, insomnia, digestive disorders, etc.digestive disorders, etc.

Review of the LiteratureReview of the Literature

Review of research literature related to Review of research literature related to medical applications of various forms medical applications of various forms of cannabis.of cannabis.

BenefitsBenefits of medical use examined, as of medical use examined, as well as, potential well as, potential risksrisks associated with associated with medical & recreational use.medical & recreational use.

Drug DeliveryDrug Delivery

MarinolMarinol (dronabinol): (dronabinol): syntheticsynthetic version version of delta-9 tetrahydrocannabinol (THC) of delta-9 tetrahydrocannabinol (THC) in sesame oil capsulein sesame oil capsule

CesametCesamet (nabilone): better absorbed (nabilone): better absorbed version of dronabinolversion of dronabinol

SativexSativex: THC + cannabidiol, : THC + cannabidiol, naturalnatural liquid marijuana extract sprayed into liquid marijuana extract sprayed into mouth-not approved in U.S.mouth-not approved in U.S.

Review of literature from past Review of literature from past 40 years40 years

164 serious adverse events among patients 164 serious adverse events among patients receiving cannabis therapy as compared to receiving cannabis therapy as compared to 60 such events in controls60 such events in controls

Adverse events included primarily Adverse events included primarily respiratory & nervous system disordersrespiratory & nervous system disorders

““short term use of existing medical short term use of existing medical cannabinoids appeared to increase the risk cannabinoids appeared to increase the risk of nonserious adverse events” of nonserious adverse events”

--Wang et al. 2008Wang et al. 2008

Meta-Analysis of Double-blind Meta-Analysis of Double-blind Randomized Controlled TrialsRandomized Controlled Trials

Medical marijuana for painMedical marijuana for pain Reviewed 93 studies (18 in final analysis)Reviewed 93 studies (18 in final analysis) Authors concluded that cannabis use in Authors concluded that cannabis use in

the treatment of pain presented more risks the treatment of pain presented more risks than benefitsthan benefits

--Martin-Sanchez et al., 2009Martin-Sanchez et al., 2009

First Study of Sativex for First Study of Sativex for Intractable PainIntractable Pain

Diabetic neuropathy, 38 patientsDiabetic neuropathy, 38 patients No more efficacious than placeboNo more efficacious than placebo Need for more researchNeed for more research

-Salvarajah et al., 2010-Salvarajah et al., 2010

Cannabis for Palliative CareCannabis for Palliative Care

Review of all literature from 1996-2010Review of all literature from 1996-2010 Authors noted “systematic reviews on the Authors noted “systematic reviews on the

efficacy of cannabis in pain control for efficacy of cannabis in pain control for humans suggests that there is as yet humans suggests that there is as yet inconclusive evidence that cannabis has inconclusive evidence that cannabis has any major therapeutic role in pain any major therapeutic role in pain management.”management.”

--Green & DeVries, 2010, p. 2457Green & DeVries, 2010, p. 2457

Positive Findings from Green & Positive Findings from Green & DeVriesDeVries

Literature suggestive of improvements Literature suggestive of improvements in Quality of Life (QOL) outcomes such in Quality of Life (QOL) outcomes such as improvements in sleep and as improvements in sleep and abatement of depressive symptoms. abatement of depressive symptoms. Also, reports on opiod-sparing effects-Also, reports on opiod-sparing effects-synergistic effects of synergistic effects of opiod/cannabinoid preparationsopiod/cannabinoid preparations

More Positive PotentialMore Positive Potential

Cesamet & Sativex potentially efficacious Cesamet & Sativex potentially efficacious as as adjuvant therapiesadjuvant therapies for secondary for secondary treatment of chronic illnesstreatment of chronic illness

Maybe subjective improvement from Maybe subjective improvement from patient’s perception for chronic painpatient’s perception for chronic pain

Patients may not perceive benefits of oral Patients may not perceive benefits of oral administrationadministration

-Peat, 2010-Peat, 2010

Sativex for Overactive Bladder Sativex for Overactive Bladder with MSwith MS

135 patients, 10 week double-blind 135 patients, 10 week double-blind randomized, placebo-controlled trialrandomized, placebo-controlled trial

Concluded Sativex did provide some Concluded Sativex did provide some improvements in QOL indicators but improvements in QOL indicators but results did not reach statistical results did not reach statistical significancesignificance..

-Kavia et al., 2010-Kavia et al., 2010

Sativex for MS related Sativex for MS related SpasticitySpasticity

Meta-analysis of 3 randomized, placebo-Meta-analysis of 3 randomized, placebo-controlled, double-blind studiescontrolled, double-blind studies

666 patients with MS-related spasticity666 patients with MS-related spasticity Large numbers of subjects experienced at Large numbers of subjects experienced at

least one adverse eventleast one adverse event Sativex did reduce spasticity & was well Sativex did reduce spasticity & was well

tolerated overalltolerated overall -Wade et al., 2010-Wade et al., 2010

““no solid conclusive data have emerged that no solid conclusive data have emerged that would justify the use of cannabis as an would justify the use of cannabis as an alternative to the currently marketed and alternative to the currently marketed and accepted therapeutic analgesic arsenal.”accepted therapeutic analgesic arsenal.”

-Martin-Sanchez et al. 2009, p. 1354-Martin-Sanchez et al. 2009, p. 1354

Risks Associated with Risks Associated with Chronic Marijuana UseChronic Marijuana Use

Marijuana Abstinence SyndromeMarijuana Abstinence Syndrome(>48 hrs-2 weeks)(>48 hrs-2 weeks)

1. irritability/anger/agitation2. anorexia3. Insomnia/vivid dreams4. depression5. anxiety6. headaches7. muscle tension

-Lamarine & Sbarbaro. 1996

Lung Damage/Heart DiseaseLung Damage/Heart Disease

Threefold increase of inhaled tar compared Threefold increase of inhaled tar compared to tobaccoto tobacco

Fivefold increase in CO (carboxyhemoglobin) Fivefold increase in CO (carboxyhemoglobin) from smoked marijuana from smoked marijuana heart disease heart disease

Depth of inhalation, volume of smoke Depth of inhalation, volume of smoke inhaled, duration of breath holdinginhaled, duration of breath holding

Evidence of obstructive lung diseaseEvidence of obstructive lung disease Concurrent use with tobacco may produce Concurrent use with tobacco may produce

synergistic effects and increase risk for synergistic effects and increase risk for COPDCOPD

CancerCancer

Inhaled smoke loaded with carcinogensInhaled smoke loaded with carcinogens Increased risk for a wide variety of Increased risk for a wide variety of

cancers in smoker and child if smoker cancers in smoker and child if smoker is pregnantis pregnant

AnxietyAnxiety

Consistent relationship between Consistent relationship between frequent marijuana use & higher frequent marijuana use & higher anxiety levels but NOT with anxiety anxiety levels but NOT with anxiety disordersdisorders

Anxiety also related to withdrawal Anxiety also related to withdrawal syndromesyndrome

-Crippa et al., 2009-Crippa et al., 2009

PSYCHOSISPSYCHOSIS

*risk for psychosis in general population <1%*marijuana users have 40% increase*heavy users 200% increase*six major studies in five countries targeting

adolescents & young adults*link only for psychosis, not anxiety, depression, or

other mental health problems*mabe pre-existing problems may lead to BOTH pot

use + psychosis?? Zammit, et al. The Lancet, July 27, 2007Also poor outcomes in schizophrenic users

ADDICTION RATES FOR USERS OF ADDICTION RATES FOR USERS OF SELECTED DRUGSSELECTED DRUGS

MARIJUANA 9%

ALCOHOL 15%

HEROIN 23%

TOBACCO 32%

ConclusionsConclusions

1. Risk/benefit outcomes inconclusive1. Risk/benefit outcomes inconclusive

2. Smoking as a delivery mechanism has 2. Smoking as a delivery mechanism has significant health risks & concerns significant health risks & concerns regarding dosage administrationregarding dosage administration

3. Clinical trials have not presented clear 3. Clinical trials have not presented clear evidence of significant efficacyevidence of significant efficacy

4. Synergistic opiod-sparing effect 4. Synergistic opiod-sparing effect appears promisingappears promising

4. Risks with “medical” use appear to be 4. Risks with “medical” use appear to be minor but not insignificantminor but not insignificant

5. Does long-term marijuana use increase 5. Does long-term marijuana use increase risk for psychosis?risk for psychosis?

6. Anxiety risks appear to be dose-related 6. Anxiety risks appear to be dose-related & of short-term duration& of short-term duration

7. Moving cannabis to Schedule II would 7. Moving cannabis to Schedule II would facilitate more researchfacilitate more research

To request a PDF of my article or Power To request a PDF of my article or Power Point on medical marijuana, send an email Point on medical marijuana, send an email to:to:

rlamarine@csuchico.edurlamarine@csuchico.edu