Psychoactive Plants

1. Psychoactive Plants Hallucinogens - I: Marijuana

2. Marijuana • Cannabis sativa is one of the oldest cultivated plants in the world • Possibly used by humans for over 10,000 yrs • Known by many names: mary jane, hashish, hash, pot, grass, hemp, etc • Native to central Asia and widely used for thousands of years: • As a hallucinogen • Medicinally • For fiber (rope, paper, fabric) - hemp • For oil and seeds

3. Early History of Marijuana • Long history of use in China (over 5000 yrs) as a medicinal plant • Scythians (nomadic tribe from central Asia) used it as a hallucinogen – about 500 BC – India maybe older • Spread throughout Asia, Africa, and elsewhere • Became prominent in India for both medical and religious use (first written account in India 600BC) • In Middle Ages widely used throughout Arab world • Most notorious story about marijuana is the fanatical Muslim sect known as Hashishins who swore to kill all Christian crusaders. Group name from hashish – also gave rise to the word assassin

4. Later History • Use in Europe limited to fiber for many years • Said that Naploen’s army introduced the psychoactive use when they returned from campaign in North Africa/Egypt • By mid-19th century Paris – Hashish had widespread use among artists and intellectuals who believed it enhanced their creative powers

5. History in North America • Marijuana was probably introduced to the United States around the turn of 20th century possibly from Mexico or the Caribbean Islands. • Mexican laborers brought the marijuana smoking habit with them when they immigrated. • In the 1920's it spread among the urban poor in the South but was not in vogue until jazz musicians popularized smoking marijuana cigarettes. • Not only was marijuana used recreationally, but it was also a popular ingredient in many over-the-counter medications.

6. US History • During the 1930's concerns about the dangers inherent in marijuana use led to the establishment of laws prohibiting its use. • The Federal Bureau of Narcotics launched an "educational campaign" to make the public aware of the dangers of marijuana use. • Campaign greatly distorted the problem and grossly exaggerated the dangers • Concerns culminated in the federal Marihuana Act of 1937 which controlled the legal sale of the plant and resulted in the virtual elimination of Cannabis from the nation's pharmacopoeia.

7. Recent History • The dramatic increase in marijuana use came about 1960's • Marijuana became the recreational drug of choice • In reaction to the pervasive usage of marijuana during the 1970's many communities relaxed their laws concerning personal use and possession • The public demand for decriminalization of marijuana usage peaked in the late 1970's and recent trends seem to be for stricter enforcement and harsher sentences for users and dealers

8. New Laws in England • In October 2001, England relaxed its marijuana laws, downgrading it from a class B to a class C drug • This means that marijuana still remains illegal but the maximum penalties for possession are greatly reduced • Also under the new law, the police will no longer able to arrest someone on the street for possession • Prosecutions will be carried out by court summons • The new law is expected to take effect in spring 2002.

9. 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

11. Female Plant Male Plant

12. 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

13. 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

14. THC Levels • The most potent varieties of Cannabis are usually grown under the hot dry conditions which seem to optimize THC production • As a result Marijuana grown in Mexico, Columbia, and India generally have higher "street value" because of its higher THC levels

15. Sensemilla varieties • Seedless strain developed illicitly in California during the 1970's thought to have the highest levels of THC • Hybrids result from crossing C. sativa and C. indica (a hardy species native to Afghanistan) • Cultivated by cloning pistillate plants in high tech indoor gardens - "Sea of Green" • Possible to bring about abundant flowering in two months

16. 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

17. Cannabinoid Receptors • Humans have cannabinoid receptors in the brain, CNS, and other tissues • Functions of these receptors and the endogenous ligands unclear • At least two subtypes of these receptors exist - CB1 and CB2 - evidence also suggests other subtypes • G-protein linked receptors

18. 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

19. Natural Cannabinoids • First natural cannabinoid discovered in 1992 • Anandamide is an endogenous ligand to the cannabinoid receptors in brain – function so far has not been determined – only moderate binding ability to CB1 • Other natural ligands have since been identified • When activated, CB1 receptors seem to suppress the neuronal release of one or more transmitters • Show some interaction with opiate receptors

20. 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

21. 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 • reduce tremors in MS patients • analgesic

22. 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

23. 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

24. 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

25. Treatment of MS • 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

26. AIDS • 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

27. Analgesic Effects • In animal tests cannabinoids are analgesic and reduce neuropathic pain • Likely similar action in humans • 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

28. New Laws • Since 1996, eight states (Alaska, California, Colorado, Hawaii, Maine, Nevada, Oregon, 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

29. 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

30. Federal Response • In response to these laws, the federal government initially threatened to prosecute any physician that prescribed marijuana to patients • This produced an uproar in the medical community • The American Medical Association indicated that physicians should be free to discuss any option that might help their patients and recommended new studies on medical uses of marijuana

31. 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

32. Marijuana and Medicine • In January 1997, the White House Office of National Drug Control Policy (ONDCP) asked the Institute of Medicine of the National Academy of Science to conduct a review of the scientific evidence to assess the potential health benefits and risks of marijuana and its constituent cannabinoids • That review began in August 1997 and culminates with 1999 book Marijuana and Medicine: Assessing the Science

33. Conclusions of NAS Study • 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).

34. 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. • Writing for the court, Justice Clarence Thomas wrote that the controlled substance statue "includes no exception at all for any medical use of marijuana."

35. Supreme Court • Although voting with the majority, three justices (John Paul Stevens, David Souter, and Ruth Bader Ginsburg) wrote a concurring opinion stating that the decision went too far. • They believe that there should have been a medical necessity option for a patient, "for whom there is no alternative means of avoiding starvation or extraordinary suffering."