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By Robert G. Bell

Robert BellMarijuana is part of mainstream America, whether through legalization, decriminalization or medical use. As we (in Colorado and Oregon) embark on one of the world’s largest, uncontrolled, observational clinical studies regarding the safety, use and abuse of cannabis, answers are needed regarding marijuana’s safety, especially fetal and adolescent development, abuse, dependence, tolerance and withdrawal, dosage, formulations, and drug-drug interactions. There is a lot of information–and misinformation–in the literature and on the Internet regarding marijuana: With over 35 million hits on Google regarding marijuana cultivation, preparations, use, abuse and legalization, just sifting through the relevant information can be a daunting task.

Medical marijuana is on the 2014 Florida ballot; so I’ve been doing some literature searches of my own.

I have also received numerous calls regarding my thoughts on the issues of legalizing marijuana. There are medical uses for marijuana, but it is the thought of this author that most marijuana use will be recreational or self-diagnosed treatment. It is my opinion that the opportunity for casual use to turn into chronic use and dependence is significant. As marijuana becomes mainstream, we need to develop educational prevention programs, especially for the young, and abuse treatment options for all. And if people prefer smoking marijuana to ingesting it, all of the associated tobacco smoking warnings are applicable to the user and those around them.

So on a periodic basis, the AAPS Blog will discuss and highlight (pun intended) the history, chemistry, pharmacology, therapeutic use, and potential for abuse of marijuana. Today we will start with a background on and history of marijuana. So grab your bongs and a box of Twinkies, and buckle your seat belt: The Pineapple Express is leaving the station.

Marijuana 101: Background and History

Marijuana has been used for about 5,000 years and was listed as a medicinal compound in the USP from 1850 until 1942. Marijuana is produced from the weedlike flowering hemp, botanically classified Cannabis sativa in 1753. (Other species include Cannabis indica and Cannabis ruderalis.)

Delta9 THCMarijuana flowers and leaves contain over 400 compounds, including a mixture of at least 70 cannabinoids, some of which are pcychoactive. The most potent psychoactive cannabinoid is Δ9-tetrahydrocannabinol (THC), which is the compound responsible for the high after consuming cannabis. Some of the other cannabinoids, which are structurally related to THC, exert different medicinal and biological effects that do not exert a psychotropic effect. Cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) are known to have potent anticancer and antipsychotic effects and are considered potential alternative treatments for Parkinson and Alzheimer diseases.

Nonpsychotropic phytocannabinoids such as cannabadiol and cannabinol have found use in neurological treatments for conditions such as epilepsy and multiple sclerosis. (Zuardi 2008 reviews the historical development of research on cannabidiol.) Cannabinoids are generally aryl-substituted meroterpenes that are lipid soluble and neutral. The concentration of THC in marijuana can range from 0.5% to 20%.

Historically, hemp has served as a major source of fiber for rope, clothing, and paper, and the seeds have been used for their oils. Cannabis for hemp use appears to have originated in China over 8,000 years ago, and there is documentation of the medicinal and religious uses in China, India, and the Middle East as early as 2,700 BC and is mentioned in the Arabian folk tales One Thousand and One Nights. (Russo 2007 surveys the history of cannabis.). Its spread westward is claimed to have come from Napoleon’s soldiers bringing hashish back from Egypt as well as the French physician Jacques-Joseph Moreau’s recreational use and popularization with Le Club des Hashichins (“Club of the Hash Eaters”) that included amoung others Victor Hugo and Alexander Dumas. Its spread to the American colonies was basically agrarian for hemp’s use in rope and clothing, which eventually fell out of favor due to the use of cotton. The social practice of smoking marijuana in
the United States is usually attributable to the Caribbean sailors and the West Indian and Mexican InterstateNarcoticsAssnCardimmigration into the United States. Since then, reefer madness has spread like wildfire. In 1937, the U.S. government passed the Marihuana Tax Act to discourage the use of marijuana, which by all accounts, did not work and was repealed in 1969.

Marijuana is currently classified by the Drug Enforcement Administration as a Schedule 1 controlled substance. As defined, a Schedule 1 controlled substance has no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse. Other examples of Schedule I substances are heroin, LSD (lysergic acid diethylamide), peyote, methaqualone, and 3,4-methylenedioxymethamphetamine (“Ecstasy”). Although marijuana is still listed as a schedule 1 narcotic, the federal government has allowed federal banks to do business with legal marijuana growers in states, indicating a potential shift in federal government policies.

After our next bong hit, the Pineapple Express moves onto Marijuana 102, the chemistry and pharmacology of marijuana.

Robert G. Bell, Ph.D., is president and owner of Drug and Biotechnology Development LLC, a consultancy to the pharmaceutical industry and academia for biological, drug, and device development.