Exploring Marijuana: History, Biochemistry, Effects, and Medical Uses

1. Psychoactive Plants Hallucinogens - I: Marijuana

2. Marijuana • Cannabis sativa is one of the oldest cultivated plants in the world • Origin • Early history • China • Scythians • Spread though Asia, Africa, and other area • Later History • North America • Recent History • New Laws in England

3. Botany of Cannabis sativa • Dioecious annual with male and female flowers on different individuals • Distinctive compound leaf with seven leaflets • The hallucinogenic properties concentrated in the resin which is produced by glandular trichomes • Maximum amount of resin on female plants, especially unfertilized female flowers

5. Female Plant Male Plant

6. Biochemistry • Hallucinogenic properties concentrated in the resin with the compound Delta-9-tetrahydrocannabinol (THC) the main psychoactive compound • THC belongs to a unique group of phenolic compounds called cannabinoids

7. THC • Concentration of THC varies greatly with the variety, sex, climate, growing conditions • Sinsemilla varieties have highest THC • Varieties cultivated for fiber (hemp varieties) have the lowest levels of THC • Potent varieties • Sensimilla hybrids result from crossing C. sativa and C. indica

8. Effects of Marijuana • Euphoria and calmness • Even moderate use impairs learning, short-term memory, and reaction time • THC is fat-soluble and accumulates in body tissues and may remain for days • One of the best studied effects is decreased sperm production • Decreased testosterone levels have also been reported

9. Cannabinoid Receptors • Humans have cannabinoid receptors in the brain, CNS, and other tissues • Functions of these receptors and the endogenous ligands not clear • At least two subtypes of these receptors exist - CB1 and CB2 - evidence also suggests other subtypes • G-protein linked receptors

10. Cannabinoid Receptors • CB1 cannabinoid receptors - most prominent in the brain and CNS and appears to mediate the psychoactive properties • CB2 cannabinoid receptors - appear to be almost exclusively expressed in the peripheral tissues - especially immune tissues and may modulate responses of the immune system

11. Natural Cannabinoids • First natural cannabinoid discovered in 1992 • Anandamide is an endogenous ligand to the cannabinoid receptors in brain – function not completely determined – apparently binds to CB1 • Other natural ligands have since been identified • When activated, CB1 receptors seem to suppress the release of one or more transmitters – glutamate, dopamine, GABA – this in turn may affect learning, movement, and memory • Show some interaction with opiate receptors

12. Cannabinoid Receptors

13. Cannabinoids • CB1 receptors are extremely abundant in the brain – more so than most other G-protein linked receptors – 10x more abundant that m opioid receptors (responsible for pain relief and euphoria from opiates) • Studied extensively in vertebrates and invertebrates – highly conserved molecule suggesting a long evolutionary history (500 million yrs) suggesting that cannabinoids play and important basic function in animal physiology

14. Medical Uses of Marijuana • Marijuana has been used as a medicinal plant by cultures throughout the world • In modern medicine, several well documented uses • glaucoma treatment • aid to chemotherapy • increase appetite in AIDS patients and senior citizens • reduce tremors in MS patients • analgesic

15. Glaucoma Treatment • Glaucoma - eye disorder characterized by increased pressure • This can damage the optic nerve and lead to blindness • Leading cause of blindness in the U.S. • Marijuana - either smoking or ingesting oral preparations can decrease ocular pressure - smoke is especially effective

16. Aid to Chemotherapy • Chemotherapy for cancer often has side effects that result in nausea, vomiting, and loss of appetite - often results in severe weight loss - patients weaken considerable - often impairing recovery • Marijuana helps offset some of these effects - and especially increase appetite • Also growing evidence of anti-cancer activity

17. Other uses for appetite improvement • AZT and other drugs used to treat AIDS result in nausea and anorexia • Like use of chemotherapy in cancer patients, this commonly causes severe weight loss which impairs the bodies ability to fight • Marijuana helps nausea and increases the appetite thereby counteracting weight loss • Anorexia also a problem in some senior citizens

18. Multiple Sclerosis • Multiple sclerosis causes the destruction of patches of myelin in the brain and spinal cord • Demyelination produces many problems, so that victims eventually cannot walk, sit up, and become crippled and bedridden often with terrible muscle spasms • No effective treatment for MS - medications provide some relief from muscle spasms; however, the drugs lead to addiction • Marijuana reduce spasms in patients with MS • Individuals using marijuana have testified that sight and walking have been regained and spasms reduced or eliminated, • There is some evidence that the progress of MS is actually retarded

19. Analgesic Effects • In animal tests cannabinoids are analgesic and reduce neuropathic pain • Likely similar action in humans • Some studies show that cannabinoids are no more effective than codeine and have enough side effects to limit their use • Further studies needed to see about use for spasticity and neuropathic pain • Recent study CB2 receptors/endorphins

20. New Laws • Since 1996, nine states (Alaska, California, Colorado, Hawaii, Maine, Nevada, Oregon, Vermont, and Washington) have enacted laws or passed referenda that effectively allow patients to use medical marijuana. • These laws permit patients to use marijuana on the advise of their physicians. • In addition Arizona passed legislation, which allows physicians to write prescriptions for medical marijuana use • Federal Response to these laws aimed at physicians • Ten other states have symbolical medical marijuana laws (support use but have not legal protection) • Twelve states have medical marijuana research laws

21. States with effective medical marijuana laws Note: Arizona has a law but it is not effective because it only permits medical marijuana use when it is prescribed but physicians cannot legally prescribe

22. Editorial in NEJM • It was wrong to prohibit physicians from helping their patients. • It called for the reclassification of marijuana as a Schedule II drug so that physicians could prescribe it when needed. • Marijuana is currently classified as a Schedule I drug which is defined as a drug with no accepted medical use and a high potential for abuse. • Schedule II drugs can be prescribed for appropriate medical applications

23. NAS Study: Marijuana and Medicine • Cannabinoids likely have a natural role in pain modulation, control of movement, and memory. • The natural role of cannabinoids in immune systems is likely multi-faceted and remains unclear. • The brain develops tolerance to cannabinoids. • Animal research demonstrates the potential for dependence, but this potential is observed under a narrower range of conditions than with benzodiazepines, opiates, cocaine, or nicotine. • Withdrawal symptoms can be observed in animals but appear to be mild compared to opiates or benzodiazepines, such as diazepam (Valium).

24. Supreme Court • In May 2001 the U.S. Supreme Court unanimously ruled that medical use of marijuana is not a valid exception to the federal law that classifies marijuana as an illegal substance. • Justice Clarence Thomas: controlled substance statue “includes no exception at all for any medical use of marijuana” • Justices Sutter, Stevens, Ginsburg: Decision went too far! • In June 2005, Supreme Court ruled that the Federal Government can prosecute medical marijuana patients even in states that have laws allowing medical marijuana use.