Advances in Medical Cannabis Research

Cannabis available to the medical user comes in two commonly available types. Marijuana (domestically produced or imported Cannabis flowers) is nearly always grown from high-THC varieties (up to 30% dry weight in trimmed female flowers)

and contains very little CBD. Very high THC with negligible CBD profiles of modern sinsemilla varieties result from marijuana growers sampling single plants and making seed selections from vigorous individuals with high levels of psychoactivity. Unique individuals may also be vegetatively propagated, thereby fixing the high-THC genotype in the clonal offspring.

Commercially available imported hashish or charas (compressed Cannabis resin) is collected from varieties that are predominantly THC (up to 10%) but that often contain up to 5% CBD as well. Imported hashish is produced by bulk processing large numbers of plants. Growers rarely make seed selections from individual, particularly potent plants, and therefore without human intervention the CBD content tends to be closer to that of THC. Hashish cultivars are usually selected for resin quantity rather than potency, so the farmer chooses plants and saves seeds by observing which ones produce the most resin, unaware of whether it contains predominantly THC or CBD. Populations grown from imported indica seeds contain approx 25% plants that are rich in CBD with little THC, 50% that contain moderate amounts of both CBD and THC, and 25% that contain little CBD and are rich in THC.* Marijuana breeders utilized only the high-THC indica individuals in crosses, thereby promoting high THC synthesis and suppressing CBD.

CBD is suspected of having modifying physiological and psychological effects on the primary psychoactive compound THC, and in a medical setting it may also have useful modulating effects on THC or valuable effects of its own. However, analytical surveys of 80 recreational and medical Cannabis varieties in the Netherlands (26) and 47 samples in California (27) show that nearly every sample contained predominantly THC with little if any CBD or other cannabinoids. Higher levels of THC (and other medically effective cannabinoid and terpenoid compounds) in medical Cannabis are healthier for patients using smoked Cannabis because they can smoke less to achieve the same dosage and effect. Recently developed mechanical resin-collecting techniques combined with high-potency Western cultivars are used to make very potent and pure hashish of more than 50% THC and almost no CBD (see Fig. 5).

Proponents of medical Cannabis, especially traditional hashish users, claim that the additional benefits of herbal preparations are a result, at least in part, of the presence of other cannabinoids such as CBD. Because THC (with traces of CBD) is the prominent cannabinoid found in most domestically produced North American and European marijuana and hashish, how will medical users gain legitimate legal access to other potentially effective cannabinoids?

13. The Future of Medical Cannabis

Cannabis breeders are continually searching for new sources of exotic germplasm and will develop new varieties that will prove particularly effective as medicines.

*The ratio of THC to CBD usually approached 1:1 in populations unselected for cannabinoid content, and the amounts of cannabinoids are rather low. Industrial hemp varieties have been selected for unnaturally low levels of THC (European Union regulations stipulate <0.3% dry weight) and much higher levels of CBD, whereas sinsemilla varieties have been selected for unnaturally high levels of THC (>20% dry weight) at the expense of CBD.

Fig. 5. Both recreational and medical Cannabis typically originate from either seeded plants used primarily for traditional hashish production or seedless plants grown primarily for "sinsemilla" marijuana and occasionally for modern hashish production. THC, A9-tetrahydrocannabinol; CBD, cannabidiol.

Fig. 5. Both recreational and medical Cannabis typically originate from either seeded plants used primarily for traditional hashish production or seedless plants grown primarily for "sinsemilla" marijuana and occasionally for modern hashish production. THC, A9-tetrahydrocannabinol; CBD, cannabidiol.

Pure indica varieties are still highly prized breeding stock, and new indica introductions from Central Asia are occasionally received. Sativa varieties from Mexico, South Africa, and Korea are gaining favor with breeders because they mature early but do not suffer from the drawbacks of many indicas. Recently, Cannabis breeders have become more interested in variations in subjective effects between different clones and are developing varieties with enhanced medical efficacy based on feedback from medical Cannabis users.

Genetic modification has also reached Cannabis. Researchers in Scotland have successfully transferred genes for gray mold resistance to an industrial hemp variety (28). Because Botrytis is one of the leading pests of Cannabis, causing crop loss and contaminating medical supplies, the transfer of resistance into medical varieties would be of great value. In addition, other agronomically valuable traits may also be transferred to Cannabis, such as additional pest resistance, increased yields of medically valuable compounds, tolerance of environmental extremes, and sexual sterility. However, so far the acceptance of genetically modified (GM) organisms has been timid. The European Union, for example, has installed strict regulations to prevent the accidental release of GM crop plants, and production of GM Cannabis in the European Union may be impractical. Cannabis presents a particularly high risk for transmitting genetically modified genes to industrial hemp crops and weedy Cannabis because it is wind-pollinated. If sterile female GM clones could be developed and used for production, then gene transfer would be blocked. Genes coding for cannabinoid biosynthesis might also be transferred from Cannabis to less politically sensitive organisms.

GW Pharmaceuticals Ltd. in the United Kingdom is engaged in the development of prescription medicines derived from Cannabis and, as part of its research program to develop novel cannabinoid medicines, supports an ongoing breeding project to develop high-yielding Cannabis cultivars of known cannabinoid profile. The aims of this research are to create varieties that produce only one of the four major cannabinoid compounds (e.g., THC, CBD, CBC, CBG, or their propyl homologs) as well as selected varieties with consistently uniform mixed cannabinoid and terpenoid profiles. These uniform profiles allow for the formulation of nonsmoked medicinal products, which can meet the strict quality standards of international regulatory authorities. A sublingual spray application of plant-derived THC and CBD began clinical trials for relief of multiple sclerosis-associated symptomology in 1999. These clinical trials have gone on to include patients with neuropathic pain and cancer pain.

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