With Guest Blogger Julie S. Green, MD, PhD, University of Colorado Denver
The psychotropic properties of marijuana (MJ), prepared from the Cannabis sativa plant, have been appreciated for thousands of years. Nearly 50 years ago, delta-9-tetrahydrocannabinol (THC) was synthesized in the laboratory and was shown soon thereafter to be the primary active ingredient (Mechoulam et al, 1967; Mechoulam and Gaoni, 1967) in MJ. The relative proportion of THC to other, less active ingredients, determines the “potency” of MJ derived from a particular strain of C. sativa and generally averages a THC content of 2-3%, though some variants specifically bred for recreational use approach 20% (Pijlman, et al, 2005).
Decades of research have associated the intake of THC (for example, via smoking MJ) with increased risk of anxiety and psychosis, the development of dependence and addiction, and appetite enhancement. THC produces these effects by binding two types of receptors found within the central nervous system and various peripheral tissues (including eccrine sweat glands). These receptors, designated CB1 and CB2, can be activated by THC, but they are also activated by endocannabinoids (ECS), compounds that are chemically related to THC but are naturally produced by the body.
ECS are related to arachidonic acid, and they bind to CB1 or CB2 to modulate a number of physiological processes such as appetite, mood, and memory, so that the body does not need exogenous MJ (or ganja, mary jane, weed, or stuff ) for stimulation. An active area of current research involves studying the effects of stimulating or inhibiting the activity of these receptors. Both CB1 and CB2 receptors are present in eccrine sweat glands. Using a viral-transformed eccrine cell line Czifra et al recently studied the effect of ECS, which suppressed proliferation and increased apoptosis of sweat cells. Interestingly, the effect was not mediated by G proteins, which usually mediate CB2 receptor responses, but were mediated by the MAP Kinase pathway, which is active in some epidermal diseases.
An unanswered question is whether there are influences, short or long-term, on eccrine sweating induced by exogenous THC in MJ users. This deserves at least taking detailed histories in dormitory rooms and coffee houses, and even direct measurement of eccrine sweat function in MJ users. Studies involving MJ administration would require institutional review board approval and approval by the US Drug Enforcement Agency (DEA).
MJ plants (Cannabis sativa) synthesize cannabinoids and produce more active THC when exposed to increased levels of UVB (Lydon et al, 1987). That is why so many UVB light bulbs are used not for tanning but for C. sativa cultivation — and why C. sativa is often grown at high elevations. The US Department of Agriculture has carefully studied the UV effects, and Lydon et al. describe detailed techniques for growing C. sativa plants. Such information suggests ambivalence on the part of the US government towards MJ — or the misperception that plant growers do not use Pubmed and Google.
The Sativa plant that produces MJ is a cultivar closely related to the sativa that produces hemp, a rather dull but commercially important product; plants in that family produce seeds that are an important oil and protein source (Pate, 1994). (The Journal of the Industrial Hemp Association, in which this report was published, had a brief life span, but discussions of the life and death of research journals is a topic for another day). While only this particular group of plants produce THC, it is unlikely that the plants use these chemicals for a high; nonetheless, the role of THC in plant ecology is uncertain. Insects do not have CB receptors, but THC may play a role in controlling competing plants, fungi and other parasites, and herbivores. THC also provides a modest sun protection factor, but sun protection is not a likely role for THC in sativa.
Many are interested in knowing whether individuals are using — or have recently used — MJ. When I enter my local Lowe’s to buy tools for my silver workshop I always notice the sign announcing that drug testing is required for employees; that assures me the employee will lead me to the correct aisle to find an odd-sized file or drill bit. And this is where hair enters to story (Huestis, 2007).
MJ is converted to polar and nonpolar metabolites, many of which enter growing hairs. There are sensitive analytical techniques for detecting THC, and hair is an archeological record of past MJ use. Incorporated THC cannot be removed by ordinary techniques available in the home or smoke-shop laboratory. Hair must be washed with lipid solvents to remove any environmental MJ contamination from the sample. There is always the possibility of sampling pubic hair to decrease the likelihood of contamination by ambient MJ, but that seems a bit intrusive. Plucked anagen hairs would allow a more timely analysis of recent MJ usage and would be a good research project for skin biologists.
Since C. sativa and THC have been interacting with humans for millennia, studying ecology and the interface between plants and humankind is a legitimate reason to be growing sativa . . . register with the DEA, get permission to grow the plants, develop testable hypotheses, publish your results, and earn credibility as a sativa ecologist. You may make lots of friends in the process.
Huestis, MA Cannabinoid Concentration in Hair from documented Cannabis users. Forensic Sci Int 169:129-136, 2007.
Lydon J et al UV-B radiation effects … Photochemistry and Photobiology 46:201-206,1987.
Pate, DW Chemical ecology of Cannabis. J International Hemp Assoc 2:29,32-37,1994.
Pijlman FT, Rigter SM, Hoek J, Goldschmidt HM, Niesink RJ. Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops. Addict Biol 10: 171-180, 2005.
Mechoulam R and Gaoni Y. The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett 12, 1109-1111, 1967.
Mechoulam R, Braun P, and Gaoni Y. A stereospecific synthesis of (-)-delta 1- and (-)-delta 1(6)-tetrahydrocannabinols. J Am Chem Soc 89: 4552-4554, 1967.
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