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By Robert G. Bell

Robert BellMarijuana affects almost every body system with many of the properties associated with alcohol, opiates, tranquillizers and hallucinogens. Marijuana can be anxiolytic, sedative, and analgesic, and can stimulate appetite. Toxicities are very low, and no deaths directly due to acute cannabis use have ever been reported.

As described previously, the term cannabis is used to describe the numerous (more than 80) compounds derived from the female plant of Cannabis sativa that have been identified and collectively referred to as cannabinoids. The most abundant cannabinoid and the primary psychoactive constituent is Δ9-tetrahydrocannabinol (THC). Other plant cannabinoids of pharmacologic interest are Δ8-THC, cannabinol and cannabidiol. The level of THC in marijuana is not always the same, and can vary depending on the strain or variety of marijuana and the way in which it is grown, harvested, prepared, and stored. The delivery of THC, through smoking, vaporization, or ingestion, also results in variations of the drug delivered and the pharmacokinetics. Although marijuana and concentrates such as hash may be eaten, they are typically smoked due to the ease and more predictable titration of THC blood levels to achieve a given psychoactive effect.

The endocannabinoid system is an evolutionarily conserved lipid-signaling system found in all vertebrates, which appears to have important regulatory functions throughout the human body. The system has been implicated in a very broad number of physiological and pathophysiological processes, including neural development, immune function, inflammation, appetite, metabolism and energy homeostasis, cardiovascular function, digestion, bone development and bone density, synaptic plasticity and learning, pain, reproduction, psychiatric disease, psychomotor behavior, memory, wake/sleep cycles, and the regulation of stress and emotional state.

The endocannabinoid system consists of cannabinoid receptors CB1 and CB2. The protein sequences of CB1 and CB2 receptors are about 44% similar. THC binds to these endogenous cannabinoid receptors and activates membrane-bound G-protein receptors, which are responsible for psychoactive effects of cannabis. The G‐protein-coupled receptors modulate the chemical reactions inside cells through cAMP, and the activity at the receptors can decrease calcium influx, increase potassium conductance and provide a neuroprotective effect on the GABA and glutamatergic systems. In general, the CB1 receptors are located in the brain and the CB2 receptors located in the peripheral nervous system. THC binding to CB1 receptors in the brain causes psychoactive effects. CB1 receptors are distributed widely throughout the central nervous system (CNS) and the peripheral nervous system (PNS) and are present in their greatest concentration around the hippocampus, cortex, olfactory areas, basal ganglia, cerebellum, and spinal cord. This association accounts for the effects of cannabinoids on memory, emotion, cognition, and movement. CB1 receptors are sparse in the brainstem, which may explain the lack of respiratory depression or death associated with the administration of high doses of these compounds. CB1 is also found on enteric nerves, which mediate gastrointestinal effects and vagal complex of brainstem to calm nausea and vomiting. CB2 is found in immune tissues and cells and may be involved in anti‐nociceptive, and anti‐inflammatory activity, since cannabinoids have immunosuppressive effects on macrophages, T‐lymphocytes and natural killer (NK) cells.

Next up is more marijuana pharmacology, including pharmacokinetics: You might need a general anaesthetic.

Robert G. Bell, Ph.D., is president and owner of Drug and Biotechnology Development LLC, a consultancy to the pharmaceutical industry and academia for biological, drug, and device development.