The Psychoactive Effects of Cannabis

FIGURE 18.1 A marijuana leaf (Cannabis sativa) used in the preparation of marijuana cigarettes. 

Tolerance to the effects of marijuana clearly exist even though chronic users have described a reversed tolerance and claim that smaller doses of the drug are necessary to produce the desired effects. This effect is probably related to the manner of use and the expectations of the user. Chronic, high-dose cannabis users may experience an abstinence or withdrawal syndrome on abrupt discontinuation of use. Signs and symptoms include irritability, restlessness, nervousness, weight loss, insomnia, and rapid eye movement (REM) rebound. Onset of this syndrome is several hours after the last dose, and it lasts 4 to 5 d. Because withdrawal is not life-threatening, treatment involves little more than supportive therapy with short-term, low doses of benzodiazepines. 

There has been much recent information on the dangers of passive tobacco smoke. Concern could also be expressed over potential problems of passive marijuana smoke, although intoxication is rarely reported from passive inhalation of marijuana. However, there are numerous reports of cannabis metabolites detected in the urine of the passive inhaler. THC metabolites may be present in the urine up to 2 months after heavy chronic use. 

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The Scythians are credited with spreading the use of cannabis to the Greeks from the steppes (Rudgiey 1993). The ancient Greeks knew of the psychoactive effects of cannabis, aithough the prevaience of its use is... 

The CBi cannabinoid receptor is the major mediator of the psychoactive effects of cannabis and its derivatives. In addition, this G protein-coupled receptor transduces many of the effects of the endogenous cannabinoids. Understanding the distribution of CBi receptors has proved helpful to both predict and understand the effects of cannabinoids. For example, the high CBi receptor levels found in cortex, basal ganglia, and cerebellum coincide with the prominent effects cannabinoids have on functions subserved by these brain regions. By comparison, the low levels present in the medullary nuclei responsible for regulating respiration are consistent with the modest effects cannabinoids have on respiratory drive. Furthermore, the strong presynaptic localization of the receptor found in ultra-structural studies underscores its major role as a modulator of neurotransmitter release. 

Cannabis sativa is the genus and species name of a flowering plant which has been used medicinally for thousands of years. Delta-9-tetrahydrocannabi-nol (A -THC) is responsible for almost all the psychoactive effects of cannabis, but is only one of more than 60 similar compounds found in cannabis which, together, are collectively known as cannabi-noids. Cannabinoid agonists that share the basic chemical structure of delta-9-tetrahydrocannabinol have been increasingly studied in recent years for potential benefits in various types of pain and pain syndromes. 

The main active ingredients of cannabis are cannabinol, cannabidiol and several isomers of tetrahydrocannabinol, of which delta-9-tetrahydro-cannabinol (THC) is probably responsible for most of the psychoactive effects of the various preparations. It is of interest to note that THC does not contain nitrogen in its three-membered ring system. The structure of THC is shown in Figure 15.8. 

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 expectations, and the user s biological vulnerability to the effects of the drug. 

A9-Tfetrahydrocannabinol (A9-THC), the psychoactive constituent of Cannabis binds to a specific G-protein coupled receptor in the brain. Although the cannabinoid receptor in the rat and in the human has been cloned, its physiological function is unknown. The well established behavioral effects of THC and the abundance and anatomical localization of the receptor in the brain suggest a role for the receptor in the control of movement, memory, emotions and pain modulation, amongst other activities. 

Marijuana Chemistry explains the psychoactive constituents of cannabis, and the effect of growth conditions, harvesting and processing, and method of ingestion on potency. This new edition of the widely respected classic features 64 pages of updates based on current research and black market studies. 

Brain cannabinoid receptor. In humans, psychoactive cannabinoids produce euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration, and impairment of memory. The cognitive deficiencies persist after withdrawal. The toxicity of cannabis has been underestimated for a long time, since recent findings revealed that A-9-THG-induced cell death with shrinkage of neurons and DNA fragmentation in the hippocampus. The acute effects of cannabinoids, as well as the development of tolerance, are mediated by G protein-coupled cannabinoid receptors. The CBl receptor and its splice variant, CBl A, are found predominantly in the brain with highest densities in the hippocampus, cerebellum, and striatum. The CB2 receptor is found predominantly in the spleen and in hemopoi-... 

Cannabis sativa plants contain at least 400 different compounds, of which as many as 60 are structurally related to 5 -tetrahydrocannabinol (5 -THC), the primary psychoactive constituent of cannabis. When cannabis is smoked, hundreds of additional compounds are produced by pyrolysis, which may contribute to both acute and chronic effects (Abood and Martin, 1992). The central nervous system actions of canna-binoids are mediated primarily through the CBj receptor. A second type of cannabinoid receptor, termed the CB2 receptor, is distributed primarily in the periphery (Gifford et ah, 1999). Activation of central cannabinoid receptors modulates neurotransmitter release at... 

Cannabinoids are the psychoactive components of marijuana, which has the species name Cannabis sativa. Concentrations of cannabinoids vary greatly from plant to plant. The original strains of this plant species contain very little of these psychoactive components and have been used for many centuries for their great fiber qualities. Strains of Cannabis that may be smoked for psychoactive effects on average contain about 4 percent cannabinoid derivatives. The most active of these derivatives is the compound A9-tetrahydrocannabinol (THC), shown in Figure 14.33 on page 504. 

Despite society s focus on the marijuana high, cannabis historically has provided many meaningful industrial and medicinal values that are not attributed to its psychoactive effects. Researchers discovered that cannabis crops farmed as far back as 12,000 years ago yielded hemp, a distinct variety of the cannabis plant associated with little or no psychoactivity. The first evidence of the medicinal use of cannabis can be traced to a Chinese health publication from... 

Paracelsus, often regarded as the father of alchemy, first became acquainted with Cannabis products while in Basel, Switzerland, where the pharmaceutical firm of Sandoz now stands. It was also there that the botanist Leonhardt Fuchs sketched a charming, classic drawing of the sativa plant in 1543- By this time, the inebriating effects of sativa % resin had been discovered by Europeans. Francois Rabelais, writing in the early sixteenth century devoted three small chapters of his Third Book of Pantegruel to this herb s botanical and psychoactive properties. 

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