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The O’Shaughnessy’s Reader | Society of Cannabis Clinicians

Everyday We Write the Book “Everyday I Write the Book” is a true song by Elvis Costello and it’s also our aim —to post news, analysis, and relevant history that people interested in the medical marijuana movement might find useful. I’ve been covering the movement in earnest since 1996, when California voters passed Proposition 15, which allowed doctors to approve cannabis use by patients. It’s a big story with many facets —science, politics, law, medicine, history, economics— and a cast of thousands, and a supporting case of millions. My day job as an editor at the University of California San Francisco enabled me to follow advances on the scientific front. And I had good connections on the political and medical fronts, including Dennis Peron —whose San Francisco Cannabis Buyers’ Club had given rise to the Prop 215 campaign— and Tod Mikuriya, MD, the Berkeley-based psychiatrist who had published the suppressed pre-prohibition medical literature on marijuana and helped draft Prop 215. In 2000 I joined the ranks of law enforcement as public information officer for the District Attorney of San Francisco, Terence Hallinan. Getting an inside view of how the “War on Drugs” is actually prosecuted —even in the city and county of San Francisco under “America’s most progressive DA”— confirmed my outside view. Two-thirds of all criminal cases involve drugs. Enforcing drug prohibition is the excuse for maintaining an outsized police force. Abolition in one county can’t be achieved. In 2003 I producedO’Shaughnessy’s in support of Dr. Mikuriya, who was being prosecuted by the Medical Board of California. Tod had organized a group of doctors (now called the Society of Cannabis Clinicians) who were monitoring cannabis use by patients. He wanted a journal that would publish the SCC doctors’ findings and observations, and keep them up-to-date on what scientists were learning about the endocannabinoid system, and report on relevant political and legal developments of interest. By design, O’Shaughnessy’s came out as a cross between a medical journal and a defense-committee leaflet. “Hybrid vigor!” Tod proclaimed. He died in 2006. The SCC abides under the leadership of Jeffrey Hergenrather, MD. O’Shaughnessy’s abides as a tabloid distributed by SCC members to their patients —and now online. Martin A. Lee has been an editor since 2009. Viewpoints expressed on this site and in O’Shaughnessy’s do not reflect positions taken by the SCC. Signed pieces present the opinions of the authors; unsigned pieces present the opinions of the editors. Contents (c) 2012 by O’Shaughnessy’s. All rights reserved. Please address reprint requests to —Fred Gardner via The O’Shaughnessy’s Reader | Society of Cannabis Clinicians.


Tetrahydrocannabinol, also known as THC, Δ9-THC, Δ9-tetrahydrocannabinol (delta-9-tetrahydrocannabinol), Δ¹-tetrahydrocannabinol (using an older numbering scheme), or dronabinol, is the main psychoactive substance found in a variety of plants; most abundantly so in the Cannabis plant. It was isolated by Raphael Mechoulam and Yechiel Gaoni from the Weizmann Institute in Rehovot, Israel in 1964. In pure form it is a glassy solid when cold and becomes viscous and sticky if warmed. THC has a very low solubility in water, but a good solubility in most organic solvents such as ethanol or hexane. As in the case of nicotine and caffeine, THC's most likely function in Cannabis is to protect the plant from herbivores or pathogens [1]. THC also possesses high UV-B (280-315 nm) absorption properties, protecting the plant from harmful radiation. Pharmacology Its pharmacological actions are the result of its binding to the cannabinoid receptor CB1, located in the brain. The presence of these specialized receptors in the brain implied to researchers that endogenous cannabinoids were manufactured by the body, so the search began for a substance normally manufactured in the brain that binds to these receptors, the so-called natural ligand or agonist, leading to the eventual discovery of anandamide, 2 arachidonyl glyceride (2-AG) and other related compounds. This story resembles the discovery of the endogenous opiates (endorphins, enkephalins, and dynorphin), after the realization that morphine and other opiates bound to specific receptors in the brain. THC has analgesic effects that, even at low doses, causes a "high", and medical cannabis can be used to treat pain. Other effects include: relaxation; euphoria; altered space-time perception; alteration of visual, auditory, and olfactory senses; disorientation; fatigue; and appetite stimulation. It also has anti-emetic properties, and also may reduce aggression in certain subjects. Toxicity According to the Merck Index, 12th edition, THC has a LD50 value of 1270 mg/kg (male rats) and 730 mg/kg (female rats) administered orally dissolved in sesame oil. If this were scaled up to an adult human, the LD50 would be between approximately 50 and 86 g for a 68 kg (150 lb) female or male person respectively. This would be equivalent to 1-1.8 kg of cannabis with a 5% THC content (roughly average) taken orally. The LD50 value for rats by inhalation of THC is 42 mg/kg of body weight. It is important to note, however, that toxicity studies in animal models do not necessarily correlate to human toxicity. THC receptor distribution in the rat CNS is different from that of humans, meaning that there is the significant possibility that toxicity in humans varies from the published animal LD50 studies. There has never been a documented fatality from marijuana or THC overdose. Absorption is limited by serum lipids which can become saturated with THC, thus the inherent solubility may mitigate toxicity. Studies of the distribution of the cannabinoid receptors in the brain explain why THC's toxicity is so low (i.e., the LD50 of the compound is so large): parts of the brain that control vital functions such as respiration do not have many receptors, so they are relatively unaffected even by doses larger than could ever be ingested under any normal conditions. Research A number of studies indicate that THC may provide medical benefits for cancer and AIDS patients by increasing appetite and decreasing nausea. It has been shown to assist some glaucoma patients by reducing pressure within the eye, and is used in the form of cannabis by a number of multiple sclerosis patients to relieve the spasms associated with their condition. Studies also indicate a variety of negative effects associated with constant, long-term use, including short-term memory loss. However, other studies have refuted this, claiming the MRIs of long term users show little or no difference to MRIs of the non-using control group. Although using positron emission tomography (PET), at least one study indicates altered memory-related brain function in marijuana users . The long-term effects of THC on humans have been disputed because its status as an illegal drug makes research difficult. Preliminary research on synthetic THC has been conducted on patients with Tourette syndrome, with results suggesting that it may help in reducing nervous tics and urges by a significant degree. Animal studies suggested that Marinol and nicotine could be used as an effective adjunct to neuroleptic drugs in treating TS. Research on twelve patients showed that Marinol reduced tics with no significant adverse effects. A six-week controlled study on 24 patients showed the patients taking Marinol had a significant reduction in tic severity without serious adverse effects. Seven patients dropped out or had to be excluded from the study, one due to adverse side-effects. More significant reduction in tic severity was reported with longer treatment. No detrimental effects on cognitive functioning and a trend towards improvement in cognitive functioning were reported during and after treatment. Marinol's usefulness as a treatment for TS cannot be determined until/unless longer controlled studies on larger samples are undertaken. Recent research has shown that many adverse side effects, generally known as the "stoner" stereotype, fail to hold up to the scientific method. Recent studies with synthetic cannabinoids show that activation of CB1 receptors can facilitate neurogeneration, as well as neuroprotection, and can even help prevent natural neural degradation from neurodegenerative diseases such as MS, Parkinson's, and Alzheimer's. This, along with research into the CB2 receptor (throughout the immune system), has given the case for medical marijuana more support. In in-vitro experiments THC at extremely high concentrations, which could not be reached with commonly consumed doses, caused inhibition of plaque formation, the cause of Alzheimer's disease, better than currently approved drugs.[8] THC may also be an effective anti-cancer treatment, with studies showing tumor reduction in mice, conducted in 1975.[9] Chemical name (−)-(6aR,10aR)-6,6,9-trimethyl- 3-pentyl-6a,7,8,10a-tetrahydro- 6H-benzo[c]chromen-1-ol Chemical formula C21H30O2 Molecular mass 314.46 g/mol Glass transition 9.3 °C Boiling point 155-157 °C (vacuum, 0.07 mbar) Solubility (water) 2.8 mg/L (23 °C) Solubility (saline) 0.77 mg/L (NaCl, 0.15 M) pKa 10.6 log P 3.78 (water @ pH 7 / octanol) CAS number 1972-08-3