Marijuana Biology


Cannabis sativa, obtained from hemp plants, is among the oldest and most widely used drugs in the world. Tetrahydrocannabinol is the major psychoactive ingredient found in marijuana.  In addition to THC, approximately 60 other cannabinoids are found in the marijuana plant.  The discovery of naturally occurring cannabinoids, endogenous cannabinoids, and two major receptors CB1 and CB2 have incited additional interest in cannabinoid pharmacology.

Patients presenting to treatment frequently have a history of cannabinoid use.  Occasionally, cannabinoids are the only drug the patient had been using prior to admission.  More frequently cannabinoids are an additional component of the patient’s drug use.  Cannabis use dates back at least 12,000 years and is believed to have started in Central Asia moving to Southeast Asia and India.  It is known to have been used by ancient Chinese and Greek civilizations.  Historians believe hemp was introduced in the 1600s by English settlers and Spanish conquistadores. The earliest references to medicinal uses are from 2700 B.C. in India and the Middle East.  In ancient China it was used for constipation, malaria, rheumatic pains and female disorders.

Cannabis popularity began to rise in the 1930s and was listed as an official drug in the US pharmacopeia from the mid-19th century until the mid-20th century.  Its medicinal use was abolished in 1937 with the Marijuana Tax Act.  Culturally, dramatic increase in cannabis use was observed in the 1960s.  National Institute of drug abuse data from the year 2000 indicate that current alcohol use was found in about half of marijuana users.  Frequently marijuana is combined with other drugs including PCP.  Pharmaceutical uses for cannabinoid derivatives are underway.

A variety of effects of cannabis have been observed including anticonvulsant, antiemetic, and antinociception (pain relieving). Some have suggested using cannabinoids as a treatment for glaucoma as well.  Antinociception effects may be mediated through dynorphin and enkephalin (the bodies’ own pain management systems) as well as the cannabinoid receptor.

Pharmacologic actions  

Discriminative ability and rapid critical judgment processing are both significantly impaired by marijuana use.  Impaired motor coordination performance, short-term memory and attention, signal detection and tracking behavior, and perception time are all decreased.  There are at least additive and possibly synergistic decreases on the performance of tasks such as driving or operating machinery when combined with other medications.

Behavioral facts may be characterized as an aide motivational syndrome.  Most of this evidence is anecdotal however patients generally have a decreasing circle of ability to perform activities.  By the time they arrive at Passages typically they have been doing far less than they were once capable of.  One of the difficulties of marijuana use by itself is that the effects are not as dramatic as those of other drug addictions.  Typically a patient with marijuana dependence will have been using it for a number of years prior to admission.  The effects on their social functioning are sometimes subtle.

Cognitive effects of marijuana include decreases in cognition and memory as evidenced by specific memory testing.  Altered sense of self, time and space perception, and depersonalization are often seen as well.  Cognitive effects are made worse with longer duration of use.  The good news is that evidence of brain damage from chronic cannabis use is not clear.

Hippocampal synapse modulation is implicated as a central mechanism of cognitive effects of THC.  The hippocampus is region of the brain responsible for the awareness of novelty (newness).  For example, if you’re sitting in a room and you hear the refrigerator turn off, shutting off the motor triggers awareness by your hippocampus of a change in external state.  This is part of why smoking marijuana is so pleasurable.  Mundane experiences such as eating food or physical or auditory sensations are made particularly pleasurable by the increased attention the hippocampus outflow provides (hence the “munchies”).  Things that are boring in other respects are perceived as intensely new and exciting person using marijuana.  The withdrawal symptoms therefore are evidenced by intense boredom.

Locations of THC effects.

Marijuana withdrawal

Dependence on marijuana typically follows a gradual increase.  Withdrawal symptoms of a physiologic nature are more difficult to demonstrate however it is my belief that there is a physiologic withdrawal syndrome associated with marijuana cessation.  One of the observable effects of marijuana on the human physiology is an increase in heart rate.  Increased heart rate is what’s used in marijuana studies tracked the effects of the drug.  Tolerance develops to the increase in heart rate over time.  There is not typically a slowing of a heart rate with withdrawal however.  Most of the symptoms associated with marijuana withdrawal are subjective.  Because of its effects on the hippocampus and the perception of novelty, people report significant decreases in their ability to enjoy ordinary things.  Food tastes flat, experiences are an interesting, and in general they feel bored.

Some of this boredom if taken to the extreme can feel frustrating.  Other facets of this intense boredom are irritability, depression, and occasionally find motor tremor. Cessation of drug use follows a typical time course of effects peaking at about 10 hours and dropping off over the next four or five days.  Well popularized in the 50s with the film reefer madness, the gateway effect has not been observed.  A far more likely candidate for gateway use is tobacco.

Sleep disturbance is a common feature of marijuana withdrawal as well.  For the first few days patients will often report difficulty falling asleep and staying asleep.  There may be some effects on the hypothalamic pituitary adrenal axis resulting in a disruption of normal circadian cycles.  Gentle reassurance and sometimes very mild sleeping agent for a few days are usually all that are required.

Pulmonary effects of marijuana use have probably been exaggerated.  Reports that smoking a single marijuana cigarette is as bad as a pack of tobacco cigarettes are exaggerated.  Some of this may be to reduce the apparent danger of tobacco smoking.  I am not exactly sure.  People who have a history of reactive airway disease such as asthma, often find a marijuana use exacerbates their pulmonary status.  Inhalers and steroids are recommended as necessary.  Patients will report increased coughing and sputum production as well.  Patients remain concerned about pulmonary status, please refer them to the physician for pulmonary testing.  We are able to do this here at Passages.

Patients should be encouraged to discuss with the treatment team their perception of the chronic effects of marijuana use on their lives.  Unfortunately, is widely believed in the world of those who use drugs that marijuana is “not that bad”. Such an attitude leads to a chronic and progressive decline in persons quality of life and eventually quantity of life.  While no specific overdoses of marijuana have been reported causing death, it is implicated in approximately 25% of all motor vehicle accidents.  Driving under the influence is not just for alcohol. What do you think about Marijuana?


Category: Drugs

About the Author: Dr. Jason Giles is certified by the American Board of Addiction Medicine and the American Board of Anesthesiology. He is a physician specializing in the treatment of drug, alcohol, and behavioral addictions. He is the founder of Haywire.

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