Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Friday, March 2, 2012

Cannabinoids and Cannabinoid Receptors

Cannabinoids are a large family of compounds, many with psychoactive properties, that emulate the effects of marijuana by acting at cannabinoid receptors in the brain and periphery. As a general rule of thumb, cannabinoid is to cannabis as opioid is to opium. 

Cannabinoid compounds can be divided into three subtypes based on their origins; Endocannabinoids occur naturally in the body and act as neurotransmitters as do endorphins. Phytocannabinoids occur naturally in plants such as marijuana - from which the term cannabinoid has been derived - (it is important to note that most plant-derived cannabinoids are highly lipophilic; or fat soluble). Synthetic cannabinoids are produced in the lab, and may be derived from a number of molecular families - similar to the classical phytocannabinoid structure or completely different.

There are 2 subtypes of cannabinoid receptor currently known: 

The cannabinoid-1 receptor (CB1)

Expressed in the brain and throughout multiple vital organs. It is activated by the endogenous cannabinoids anandamide and 2-arachidonoyl-glyceride (2AG), as well as other exogenous cannabinoids present in marijuana. The CB1 receptor is responsible for most of marijuana's psychoactivity; namely its euphorigenic, analgetic, psychotomimetic/antipsychotic and anticonvulsant effects.

CB1 receptors are expressed presynaptically on GABAergic and glutamatergic neurons throughout the brain and when activated, serve to inhibit the release of GABA or glutamate; reducing glutamate activity causes reduced excitation, while reducing GABA activity results in a short term form of plasticity which leads to increased excitation at the post synaptic cell.

Expression of CB1 receptors has been noted in the olfactory bulb, hippocampus, amygdala, ganglia, basal ganglia, thalamic and hypothalamic nuclei - along with other subcortical areas, the cerebellum, periaqueductal grey region and the liver, lungs, and kidneys. CB1 is one of the most widely expressed G-protein coupled receptors known in the brain.

The cannabinoid-2 receptor (CB2)  

Expressed throughout the immune system and hematopoietic stem-cells. 2AG (mentioned above) is the primary endocannabinoid ligand for this receptor. CB2 receptors are responsible for the anti-inflammatory and autoimmune effects of marijuana.

Some Common Cannabinoids:



2-arachidonoyl-glycerol (2-AG)

Plant Derived:

tetrahydrocannabinol - CB1 & CB2 partial agonist

cannabinol - CB1 & CB2 weak agonist

cannabidiol - 5HT1A (serotonin) receptor agonist, indirect cannabinoid antagonist effects


nabilone - CB1 agonist (not further specified)

JWH-018 - CB1 & CB2 full agonist

JWH-210 - CB1 & CB2 full agonist

WIN-55,212-2 - Potent CB1 full agonist

AM-411 - Potent and selective CB1 full agonist

Medicinal Use:

Pharmaceutical THC (or dronabinol) is government approved in the US for use in treating anorexia in AIDS patients and severe nausea & vomiting in chemotherapy patients. When produced synthetically rather than derived from cannabis, THC is listed as a schedule III substance under the US Controlled Substance Act, placing it in the same category as buprenorphine, hydrocodone & codeine compounds such as Vicodin or Tylenol #3, and some mild amphetamine-type stimulants used as anorectics. The CIII status allows for less stringent regulations on its clinical use; for instance, a prescription for dronabinol can be called into a pharmacy by phone and written with limited refills (5 refills, or up to 6 fills total).

Nabilone is a synthetic cannabinoid which is also used clinically. Unlike Dronabinol, nabilone is a schedule II drug under the Controlled Substance Act, and therefore has heavy restrictions on its use. Nabilone is marketed under the trade name Cesamet, FDA approved for use as an antiemetic (anti-nauseant) in chemotherapy patients or in the treatment of anorexia in AIDS patients.


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