Cannabis administration routes

The effects of cannabis on cognition is a complicated issue. Numerous studies have been conducted to measure the mental effects of cannabis, but many of these are fraught with methodological problems. Several variables must be controlled in this type of research, including the dosage and potency of cannabis used, route of administration (e.g., smoking, oral, etc.), chronicity of dose, and the subject population (nonusers, occasional users, chronic users) employed (table 10.7). Population makeup has a large effect on outcome because there have been differences demonstrated between naive and experienced cannabis users (Murray 1986). 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

One particular feature of plant-derived cannabinoids is their high lipid solubility, which indicates that limited gastrointestinal absorption and bioavailability are significant barriers to their development as therapeutics. For this reason cannabis is traditionally smoked, providing the most predictable and titratable route for administration. For therapeutic development pulmonary deliveries of cannabinoid aerosols are under investigation as an alternative. 

The human data, as well as the animal studies indicate that cannabinoids may ameliorate some symptoms of MS. Unfortunately, a definitive large-scale study has yet to be performed. Such a study should take into account that (a) the placebo effect in MS is very high (b) the effective doses recorded are close to, or identical with the doses that cause cannabimimetic effects (c) cannabis (marijuana, hashish) is obviously not identical to zf9-THC, and that other constituents may synergize THC action (d) smoking cannot be compared with oral administration, and (e) the anal route of administration [141] may be a preferred one. 

Many variables affect the psychoactive properties of cannabis, including the potency of the cannabis used, the route of administration, the smoking technique, the dose, the setting, the user s past experience, the user s... 

Cannabis may be administered by inhalation or ingestion. The flowering tops or leaves are chopped and rolled in cigarette paper for smoking, or are added to food. The effects of intoxication vary with the dose and route of administration. The effects are... 

Cannabis can also be administered orally, although this route of administration is now rarely used experimentally. Marijuana plant material is crushed into a powder, which then is baked into a brownie or similar easily consumed food (14). 

Cannabis is well known to stimulate appetite (61-64). There is evidence that suggests that cannabinoid-induced enhancement of appetite is selective for snack foods (62,65). Thus, in human studies the use of higher doses of cannabinoids as well as different routes of administration, including the rectal (66) or the sublingual (67) route, should be further investigated. 

However, the problem with hashish and marijuana as a medication is their route of apphcation and their standardisation. Resorption kinetics and bioavail-abftity are highly dependent on the administration form. In addition, the content of active ingredients in cannabis fluctuates considerably, what makes it hard to compare data from different chnical studies, apart from any potential planning errors that may also have occiured. Microbial pollutants, which lead to allergies and breathing illnesses, pose another problem. AH this favours the chemical total synthesis of the pure active material. Thereby, a targeted co-administration of several cannabinoids may become feasible in the future. 

Intake of cannabis can not be confirmed by analysis of urine samples based upon detection of A -tetrahydrocannabinol ( THC), the psychoactive constituent of the drug. It has been shown that the drug is almost completely metabolized in human after i.v. administration of radiolabelled A -THC (1-3). The major excretion route was via faeces. An active metabolite, 7-hydroxy-A -THC, constituted 20% of the faecal radioactivity, but only trace amounts were present in the urine in which acidic metabolites accounted for the major part. Less than 0.02% of the administered dose of A -THC was excreted unchanged via urine. 

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