Opiates and youBy Steven Malins

Morphine and other opiates are used extensively in our society

As biologists we must decide when and how to use them

Though useful as painkillers, opiates have drastic negative

effects

Understanding how opiates work mitigates risk and enhances

benefits

We must examine the effect and action of opiates

Doctors use opiates for a

variety of reasons

Opiates reduce pain from trauma

• Morphine and derivatives are used to treat pain such as long bone fractures, and other injuries with significant pain

• Side effects include nausea, dependence on the drug, and respiratory depression

• Despite side effects, opiates like morphine are some of the best painkillers available to medical professionals.

Opiates can be used to treat chronic pain

• Along with acute pain from trauma, opiates are used to treat many disorders with chronic pain

• Doctors in the US and UK advise the use of morphine or other opiates for the treatment of vaso-occlusive crises associated with sickle cell disease

Solomon, Lawrence (2006). Treatment of pain due to vaso-occlusive crises (VOC) in adults with sickle cell disease (SCD): Limited awareness of available guidelines. 48th Annual Meeting of the American-Society-of-Hematology

Opiates may help treat cancer

• Opiates have a wide range of effects besides acting as analgesics

• They negatively regulate many cell processes, in several of the bodies tissues

• Opiates were found to decrease growth of Hepatocellular carcinoma and cause apoptosis in these tumor cellsNotas, G et all (2007). The inhibitory effect of opioids on HepG2 cells is mediated via interaction with somatostatin receptors. European Journal of Pharmacology 555(1)

Opiates cause widespread

changes in the body

Opiates act on G-Protein linked receptors

• Opiate drugs act on membrane receptors that are linked with protiens that use GTP– These proteins are called G protien coupled receptors

(GPCRs)

• It has been shown that these receptors have multiple active states, not just a single activated state– These different states are believed to be caused by

different opiates and may be the key to minimizing side effects

Pineyro, G, Elodie Archer-Lahlou (2007). Ligand-specific receptor states: Implications for opiate receptor signalling and regulation. Cellular Signalling 19 (1)

Opiates cause GI problems including constipation

• Among the other negative side effects of opiates is their depression of the Gastro Intestinal system causing constipation

• The enteric nervous system(ENS) is located in the digestive tract and it manages propulsion through the intestines

• Opiates act on opioid receptors and ophianin FQ/nocieptin receptors in the ENS inhibiting GI functionality.

Bohn, L, Kirsten Raehal (2006). Opioid receptor signaling: relevance for gastrointestinal therapy. Current opinion in Pharmacology vol 6 (6)

Opiates affect gene expression in the hippocampus

• Opiate addiction is often long term and recovering addicts report cravings long after use is discontinued.

• Studies in rats have shown that at least 20 genes show differential expression after exposure to morphine– This data was gathered by a cDNA

comparison of hippocampus’ of the rats

Marie-Claire et al (2007). Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus. Neuropharmacology 52(2)

Discontinuing opiate use is difficult

Opiates affect gene expresion

• Morphine causes gene expression changes in neuron cells and other cells in the body

• These genes affect cell growth and death, and cell morphology as well as neuron excitability

• Many of these changes, while relatively quick to take place once on morphine, take time to reverse– Thus the body response with cravings for morphine

long after its use is discontinued

McClung, C.A. (2006). The molecular mechanisms of morphine addiction. Reviews in the Neurosciences 17 (4)

Withdrawal symptoms are unpleasant

• Between 8 and 12 hours after taking heroin, or other opiates, individuals experience:– Watery eyes, yawning, sweating– Restlessness, insomnia, bone and joint pain

• Symptoms peak between one and two days after the last dose

• Though symptoms of withdrawal dissipate after about 10days, cravings and fatigue continue.

Mattick, R.P., Wayne Hall. (1996) Are detoxification programmes effective? The Lancet 347 pp97-100

Our brains associate related experiences with the “high” of

morphine• Opiates like morphine trigger the “reward”

mechanism of our brain– In the limbic system– This is asociated with feelings of euphoria

• It has been shown in mice, which are a model organism for humans, that locations where morphine was administered triggered the reward response even when there was no drug being administered.German, P.W. and Howard L. Feilds (2006). Rat Nucleus Accumbens Neurons Persistently Encode Locations AssociatedWith Morphine Reward. Journal of Neurophysiology 97

We now have the tools and

knowledge to understand

opiate’s affects

Only with continued research can we learn to use opiates

more effectively

Research must continue on medicines like morphine

You will be the ones doing such research

Image credits, in order of use• J.J. (2005) Mad scientist caricature Retrieved May 04 2007 from

http://commons.wikimedia.org/wiki/Image:Mad_scientist_caricature.png • Theo (1999) The final solution med Retrieved May 04 2007 from

http://commons.wikimedia.org/wiki/Image:The_final_solution_med.jpg • Felix Plasser (2007) 3D structural formula of morphine Retrieved May 04

2007 from http://commons.wikimedia.org/wiki/Image:MorphinPyMOL.png • Public domain, from US Department of Agriculture.• Ignis (2005). Drug ampoule Retrieved May 04 2007 from

http://commons.wikimedia.org/wiki/Image:Drug_ampoule_JPN.jpg • Albrecht Durer (1471-1528). Anatomy and geometrical proportions

Retrieved May 04 2007 from http://commons.wikimedia.org/wiki/Image:Anatomical_and_geometrical_proportions_-_Albrecht_Dürer.png

• Pollo Telescopic aerial platform unit Helsinki H16 Retrieved May 04 2007 from http://commons.wikimedia.org/wiki/Image:H16_training.jpg

• Microsoft clip art included with PowerPoint• J Rawls (2005) What's behind me Retrieved May 04 2007 from

http://commons.wikimedia.org/wiki/Image:Car_side_mirror_sunset.jpg