The cannabis plant and history of medical use

Cannabis grows profusely in most regions of the world, and has been used for millennia to produce fiber and rope.

In the early 19th century, Europe wasamong the last civilizations to encounter the plant, with diverging reasons for using cannabis.

In France,the psychoactive effects of cannabis were pursued, whereas in England the use of cannabis focused onmedical purposes.

Cannabis extracts were listed in the British, and later in the US Pharmacopeia (1850),for sedative and anticonvulsant effects. Within a century, the British and then the US Pharmacopeiaremoved cannabis listings (1932, 1941, respectively).

This was a result of the variable composition of plant preparations, short shelf-life, unpredictable doses, along with becoming overshadowed by newer,more targeted, effective pure drugs prescribed at known and reliable doses.

Subsequently, the risks of abuse, intoxication, and other negative consequences of cannabis consumption led to restrictive laws prohibiting the growth, possession and consumption of cannabis.

In the twenty first century, cannabis is still consumed using traditional methods, including rolling a blunt, glass water pipes and pipes in general. However, there is a growing trend of vaping cannabis dry herbs. Cannabis CBD consumers use a CBD vape pen to exclusively consume CBD, which uses CBD oil cartridges. THC users consume THC via vaping cannabis dry herbs. Many Americans visit blaze4days for cannabis information, including information on cannabis and cancer anorexia.

The movement to revive cannabis as a medicine is driven by multiple factors, many beyond the domain of science.

One propellant of the movement is the inadequate relief of current approaches for individuals harboring a number of debilitating chronic diseases or symptoms, including Multiple Sclerosis, Crohn’s disease, Alzheimer’s disease, cancer, and chronic pain. These and other medical conditions are frequently cited by proponents of cannabis for medical use.

Unresolved and critical questions persist: Is cannabis a safe and effective medicine for one or all of these conditions?

For all people of all ages? For chronic use? For medical conditions characterized by cognitive impairment?

Before addressing these central questions, it is essential to discuss cannabinoid chemistry and to survey endocannabinoid biology and function, as it is the foundation of claims for cannabis use innumerous medical conditions.

Cannabis chemistry, preparation

Known chemistry of Cannabis sativa The principal cannabinoids in the cannabis plant include THC, CBD, and cannabinol (CBN). THC is theprimary psychoactive compound, with CBD, a non-psychoactive compound, ranking second.

Generally,THC is found at higher concentrations than CBD, unless the ratio is deliberately altered. The known chemical composition of Cannabis sativa is constantly changing.

New non-cannabinoid and cannabinoid constituents in the plant are discovered frequently.

From 2005 to present, the number of cannabinoids identified in the whole plant increased from 70 to 104, and other known compounds in the plant increased from ~400 to ~650.3,15,16 THC levels are also shifting, as breeding of different strains are yielding plantsand resins with dramatic increases in THC content over the past decade, from ~ 3% to 12-16% or higher(w/w or percent THC weight/per dry weight of cannabis) and differing in different countries.

In some cannabis preparations, THC levels have risen even more radically by using a concentrating process(butane hash oil) that yields levels approaching 80% THC.

In an unregulated environment, other factorssuch as soil quality, bacterial and fungal contamination, the use of herbicides, pesticides, insecticides,water, light, soil availability or quality, temperature, bacterial or viral contamination, animal waste,insects, toxic chemicals, active compounds, heavy metals, bear on cannabis quality.

Dose and dose delivery via different routes (smoking, vaporizers, edibles)Cannabis is consumed by various routes, with the most common route smoking, 24 followed by vaporization, and then by the oral route. Cannabis products may be taken by ingesting edibles, sublingualor rectal administration, via transdermal delivery, eye drops and aerosols. However, few studies have documented their pharmacokinetics.

Inhalation by smoking or vaporization releases maximal levels of THC into blood within minutes,peaking at 15-30 minutes, and decreasing within 2-3 hours.

Even with a fixed dose of THC in a cannabis cigarette, THC pharmacokinetics and effects vary as a function of the weight of a cannabis cigarette itspreparation, the concentration of other cannabinoids, the rate of inhalation, depth and duration of puffs,volume inhaled, extent of breath-holding, vital capacity, escaped smoke and dose titration.

Anextensive comparison of smoke (mainstream: smoke exhaled by a smoker and sidestream: smokegenerated from the end of a cigarette) generated by igniting cannabis and tobacco cigarettes, showed marked qualitative similarities in specific compounds (e.g. ammonia, carbon monoxide, hydrogencynanide, among others), and also significant quantitative differences.

The presence, in mainstream or side stream smoke of cannabis cigarettes, of known carcinogens and other chemicals implicated in respiratory diseases is an important consideration when evaluating the safety and risks associated with cannabis smoking.

Lower temperature vaporization of cannabis has been postulated as safer than smoking, as it may deliver fewer high molecular weight components than smoked cannabis. Increasingly, delivery of cannabis to the brain for medical or recreational use is via cannabis vaporization.

Heating cannabis at moderate temperatures produces a fine mist of cannabis vapors that are inhaled via electronic cigarettes,30,31 a delivery method that elicits a similar response while reducing exposure to pyrolytic byproducts.

Vaporization reduces the characteristic odor of cannabis smoke, enabling diminished awareness by others

Hashish is a compacted resin of the plant, usually ingested or smoked. Hashish oil, a solvent-extracted liquid, is consumed by smoking or inhalation vaporization or as a food additive.32 Users report more addictive behaviors and withdrawal symptoms with the high THC levels in this preparation.

Oral ingestion from edibles is a slow absorption process and varies with the ingested matrix, as bio availability is low (10-20%).

Nevertheless, this does not result in a loss of pharmacological activity, because themajor first-pass metabolite, 11-OH-THC, is also psychoactive.

Oral ingestion delays the psychoactive effects to 30-90 minutes, with peaks at 2-3 hours and effects lasting for longer periods of time (4-12hours), depending on THC levels.

33Smoking multiple cannabis cigarettes or chronic long term use leads to higher maximal concentrations,longer duration in blood, and longer biological half-life, compared with smoking a single cigarette or infrequent smoking.

Chronic, frequent cannabis smokers’ exhibit extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden.

Lipophilicity of THC accounts for its accumulation after chronic repeated use.34,35,36,37,38 Metabolic elimination of THC from newly smoked cannabis is much slower after years of heavy cannabis use.

When a single 6.8% THC cannabis cigarette was administered to frequent and to occasional users, plasma THC concentrations were significantly higher in frequent smokers than in occasional smokers at most time points from 0.5 to 30 h.

Median(range) time of last detection was 3.5 h (1.1 to .30 h) in frequent smokers and 1.0 h (0-2.1 h) in occasional smokers. In chronic heavy (daily) cannabis users, THC can be detected in blood during a month of sustained abstinence. These findings are consistent with THC lipophilicity and time course of persisting neurocognitive impairment reported in recent studies.