Cannabinoid
Pharmacology
### Pharmacology

Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the [liver](/wiki/Liver "Liver"), especially by [cytochrome P450](/wiki/Cytochrome_P450 "Cytochrome P450") mixed\-function oxidases, mainly [CYP 2C9](/wiki/CYP_2C9 "CYP 2C9"). Thus supplementing with CYP 2C9 [inhibitors](/wiki/Enzyme_inhibitor "Enzyme inhibitor") leads to extended intoxication.

Some is also stored in [fat](/wiki/Adipose "Adipose") in addition to being metabolized in the liver. Δ9\-THC is metabolized to [11\-hydroxy\-Δ9\-THC](/wiki/11-Hydroxy-THC "11-Hydroxy-THC"), which is then metabolized to [9\-carboxy\-THC](/wiki/11-nor-9-Carboxy-THC "11-nor-9-Carboxy-THC"). Some cannabis [metabolites](/wiki/Metabolite "Metabolite") can be detected in the body several weeks after administration. These metabolites are the chemicals recognized by common antibody\-based "drug tests"; in the case of THC or others, these loads do not represent intoxication (compare to ethanol breath tests that measure instantaneous [blood alcohol levels](/wiki/Blood_alcohol_level "Blood alcohol level")), but an integration of past consumption over an approximately month\-long window. This is because they are fat\-soluble, [lipophilic](/wiki/Lipophilic "Lipophilic") molecules that accumulate in fatty tissues.

Research shows the effect of cannabinoids might be modulated by aromatic compounds produced by the cannabis plant, called [terpenes](/wiki/Terpenes "Terpenes"). This interaction would lead to the [entourage effect](/wiki/Entourage_effect "Entourage effect").

#### Modulation of mitochondrial activity

Recent evidence has shown that cannabinoids play a role in the modulation of various mitochondrial processes, including intracellular calcium regulation, activation of apoptosis, impairment of electron transport chain activity, disruption of mitochondrial respiration and ATP production, and regulation of mitochondrial dynamics. These processes contribute to various aspects of cellular biology and can be modified in response to external stimuli. The interaction between cannabinoids and mitochondria is complex, and various molecular mechanisms have been proposed, including direct effects on mitochondrial membranes and receptor\-mediated effects. However, an integrated hypothesis of cannabinoids' actions on these processes has yet to be formulated due to conflicting data and the complexity of the pathways involved.

#### Cannabinoid\-based pharmaceuticals

[Nabiximols](/wiki/Nabiximols "Nabiximols") (brand name Sativex) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC. Also included are minor cannabinoids and [terpenoids](/wiki/Terpenoids "Terpenoids"), [ethanol](/wiki/Ethanol "Ethanol") and [propylene glycol](/wiki/Propylene_glycol "Propylene glycol") [excipients](/wiki/Excipients "Excipients"), and peppermint flavoring. The drug, made by [GW Pharmaceuticals](/wiki/GW_Pharmaceuticals "GW Pharmaceuticals"), was first approved by Canadian authorities in 2005 to alleviate pain associated with [multiple sclerosis](/wiki/Multiple_sclerosis "Multiple sclerosis"), making it the first cannabis\-based medicine. It is marketed by Bayer in Canada. Sativex has been approved in 25 countries; clinical trials are underway in the United States to gain FDA approval. In 2007, it was approved for treatment of cancer pain. In Phase III trials, the most common adverse effects were dizziness, drowsiness and disorientation; 12% of subjects stopped taking the drug because of the side effects.

[Dronabinol](/wiki/Dronabinol "Dronabinol") (brand names Marinol and Syndros) is a delta\-9\-THC containing drug for treating [HIV/AIDS](/wiki/HIV/AIDS "HIV/AIDS")\-induced [anorexia](/wiki/Anorexia_%28symptom%29 "Anorexia (symptom)") and [chemotherapy\-induced nausea and vomiting](/wiki/Chemotherapy-induced_nausea_and_vomiting "Chemotherapy-induced nausea and vomiting").

The [CBD](/wiki/Cannabidiol "Cannabidiol") drug Epidiolex has been approved by the [Food and Drug Administration](/wiki/Food_and_Drug_Administration "Food and Drug Administration") for treatment of two rare and severe forms of [epilepsy](/wiki/Epilepsy "Epilepsy"), [Dravet](/wiki/Dravet_syndrome "Dravet syndrome") and [Lennox\-Gastaut](/wiki/Lennox-Gastaut_syndrome "Lennox-Gastaut syndrome") syndromes.

[Nabilone](/wiki/Nabilone "Nabilone") (Cesamet) is an FDA approved synthetic analog of THC, prescribed for the treatment of nausea and vomiting induced by chemotherapy treatment in people who have failed to respond adequately to conventional antiemetic treatments.


Can cannabinoids be detected weeks after administration?