Cannabis Active Compounds
By Diana Hahn and Stacey Marie Kerr, MD
Cannabis is a complex plant medicine containing over 100 known compounds. While there is research and information available on some of these compounds, such as THC and CBD, the vast majority of others are just beginning to be identified and understood.
The active ingredients in cannabis that have been studied to date include many cannabinoids and terpenes. Terpenes are the chemicals that give cannabis its odor and they appear to be as important medicinally as are the cannabinoids.
Adding to this complexity is the fact that many of these compounds work together to create an “entourage effect,” enhancing and/or balancing effects. For example, CBD has been shown to positively compliment THC and counteract many of the unwanted side effects experienced by patients medicating with 100% THC. Although compound interactions are not completely understood, it appears that it may be important to take cannabis in whole plant, or at least plant-derived forms, in order to preserve the complexity of these relationships and the efficacy of the medicine.
The cannabinoids and terpenes touched on below represent those that are best understood and regularly occur in the largest amounts, but do not encompass the totality of compounds present in cannabis.
Cannabinoids
Cannabinoids are compounds that interact with the endocannabinoid system within the human body.
CBGA (cannabigerol acid) and CBG (cannabigerol)
CBGA is the primary cannabinoid from which all others derive. Typically, it comprises less than 2% at harvest. The plant first makes CBGA and then converts it, sometimes in several sequential steps, into CBG, THC, CBD, and CBC. CBG is a non-psychoactive cannabinoid. While it is less commonly known than THC and CBD, it has many documented benefits.
CBG’s therapeutic qualities and uses include:
Anti-depressant via 5-HT1A antagonism (Cascio et al, 2010)
Analgesic (Cascio et al, 2010 (patented for this use in 2006)
Anti-bacterial - effective against MRSA (Appendino et al, 2008)
Anti-anxiety – GABA uptake inhibitor (Banerjee et al, 1975)
Anti-fungal (ElSohly et al, 1982)
Anti-prostate cancer (De Petrocellis et al, 2011)
Psoriasis adjunctive therapy (Wilkinson and Williamson, 2007)
Bone cell stimulant
Growth inhibitor of epithelial cancers
Anti-inflammatory
THC (delta-9-tetrahydrocannabinol)
and THCA (tetrahydrocannabinolic acid)
THCA is the most abundant cannabinoid present in most raw, unheated cannabis available today. THCA is non-psychoactive, however it converts to the psychoactive compound THC when heated. A large fraction (but not all) of THCA converts to THC upon strong heating. The amount converted depends on temperature and time. THC only occurs in small amounts in raw, unheated flowers, with most of the THC that is metabolized during consumption coming from the decarboxylation of THCA.
THC’s therapeutic qualities and uses include:
Analgesic via CB1 and CB2 receptors (Rahn and Hohmann, 2009)
Anti-inflammatory and antioxidant (Hampson et al., 1998)
Bronchodilation (Williams et al., 1976)
Slows Alzheimer’s Disease progression (Volicer et al., 1997; Eubanks et al., 2006)
Benefit on duodenal ulcers (Douthwaite, 1947)
Muscle relaxant (Kavia et al., 2010)
Antipruritic (anti-itch) for cholestatic jaundice (Neff et al., 2002)
Anti-bacterial
Anti-emetic
Anti-tumor (high dosage)
Appetite stimulant (low dosage)
Neuroprotective
Anti-proliferative
CBD (cannabidiol) and CBDA (cannabidiolic acid)
CBD is currently the second-most studied cannabinoid present in cannabis. CBDA is the main constituent in raw cannabis that is CBD-dominant. When heated, CBDA converts to CBD, similarly to the way THCA converts to THC. Both CBDA and CBD are non-psychoactive, however some CBD can be converted to psychoactive THC when ingested.
CBD’s therapeutic qualities and uses include:
Anti-inflammatory and antioxidant (Hampson et al., 1998)
Agonist on GPR55 and GPR 18, possibly supporting a therapeutic role in disorders of cell migration, notably endometriosis (McHugh et al., 2010)
Anti-anxiety via 5-HT1A (Russo et al., 2005)
Anticonvulsant (Jones et al., 2010)
Cytotoxic in treating breast cancer (Ligresti et al., 2006)
Anti-metastatic in breast cancer (McAllister et al, 2007)
MRSA treatment (Appendino et al., 2008)
Decreases sebum/sebocytes (Biro et al., 2009)
Treatment of addiction
Anti-bacterial
Lowers blood sugar levels
Anti-ischemic
Neuroprotective
CBDA’s therapeutic qualities and uses include:
Anti-inflammatory
Anti-proliferative
CBC (cannabichromene)
Less is understood about CBC than CBD or THC, however it appears that CBC may exert its effects through non-cannabinoid receptors. CBC is non-psychoactive, meaning it does not effect the mind, mood or mental capabilities.
CBC’s therapeutic qualities and uses include:
Anti-anxiety
Anti-inflammatory
Antimicrobial
Analgesic
Bone cell stimulant
CBN (cannabinol)
CBN is a mildly psychoactive compound produced by the degradation of THC.
CBN’s therapeutic qualities and uses include:
Sedative (Musty et al., 1976)
MRSA treatment (Appendino et al., 2008)
TRPV2 agonist in treating burns (Qin et al., 2008)
Inhibits keratinocyte proliferation in psoriasis treatment (Wilkinson and Williamson, 2007)
Breast cancer resistance protein (Holland et al., 2008). Breast cancer resistance protein creates resistance to chemotherapeutic agents such as mitoxantrone, topotecan and methotrexate by pushing these compounds out of the cell. CBN (at very high concentrations) can inhibit this protein, making CBN a possible adjunctive treatment.
Analgesic
Anti-bacterial
Anti-spasmodic
THCV (tetrahydrocannabivarin)
THCV is a minor cannabinoid that does not occur in all strains of cannabis. In low doses, THCV is non-intoxicating. In higher doses, however, it can create intoxicating effects similar to THC. It may also intensify the euphoric effects of THC, though the effect doesn’t last as long.
THCV’s therapeutic qualities and uses include:
Reduces panic attacks
Appetite suppressor
Bone cell stimulant
Metabolic syndrome treatment (Cawthorne et al., 2007)
Anticonvulsant (Hill et al., 2010)
Terpenes
Terpenoids are a very large class of naturally occurring organic chemicals that come in thousands of varieties.
They contribute to scents, flavors, and colors in all kinds of plants. For example, cinnamon, lavender and ginger all have different terpene profiles. Terpenes contribute to not only the bouquet of cannabis flowers, but to the therapeutic effects of cannabis as well, especially when synergistic with the cannabinoids.
Alpha Pinene
The bouquet of alpha pinene is described as pine and turpentine, and is found in pine needles and rosemary as well as cannabis.
Therapeutic qualities and uses include:
Anti-inflammatory via PGE-1 (Gil et al., 1989)
Bronchodilatory in humans (Falk et al., 1990)
Memory aid; acetylcholinesterase inhibitor (Perry et al., 2000)
Anti-bacterial
Anti-fungal
Beta Caryophyllene
Beta caryophyllene’s bouquet is woody, dry, and spicy and is present in black pepper, hops, rosemary, cloves. It is the only terpene known to interact with the endocannabinoid system directly.
Therapeutic qualities and uses include:
Anti-inflammatory via PGE 1, comparable to phenylbutazone (Basile et al., 1988)
Anti-malarial (Campbell et al., 1997)
Selective CB2 agonist, 100 nM (Gertsch et al., 2008)
Possible anti-itch properties (Karsak et al., 2007)
Possible treatment for addiction (Xi et al., 2010)
Analgesic, anti-bacterial, anti-fungal, anti-tumor
Linalool
The bouquet of linalool is floral and spicy, and is also found in lavender and freesia.
Therapeutic qualities and uses include:
Sedative in mice (Buchbauer et al.,1993)
Anti-anxiety (Russo, 2001)
Local anesthetic (Re et al., 2000)
Analgesic via adenosine A2A (Peana et al., 2000)
Anticonvulsant and anti-glutamate (Elisabetsky et al., 1995)
Potent anti-leishmanial (do Socorro et al., 2003)
Myrcene
The bouquet of myrcene is musky, earthy, and herbal with notes of citrus and clove. Myrcene is the most prevalent terpene in cannabis, and is also found in hops, lemongrass, and thyme.
Therapeutic qualities and uses include:
Anti-inflammatory via PGE-2 (Lorenzetti et al., 1991)
Sedative, muscle relaxant, hypnotic (do Vale et al., 2002)
Analgesic, antagonized by naloxone (Rao et al., 1990)
Blocks hepatic carcinogenesis by aflatoxin (de Oliveira et al., 1997)
Increases the blood-brain barrier’s permeability to THC, increasing THC’s psychoactive effects
Limonene
Limonene has a citrus rind bouquet, and is found in peppermint, rosemary, and juniper as well as citrus fruits and cannabis.
Therapeutic qualities and uses include:
Anti-anxiety (Carvalho-Freitas and Costa, 2002; Pultrini Ade et al., 2006) via 5-HT1A (Komiya et al., 2006)
Potent AD/immunostimulant via inhalation (Komori et al., 1995)
Apoptosis of breast cancer cells (Vigushin et al., 1998)
Active against acne bacteria (Kim et al., 2008)
Dermatophytes (Sanguinetti et al., 2007; Singh et al., 2010)
Gastro-esophageal reflux (Harris, 2010)
Alpha Humulene
Humulene’s bouquet is robust, earthy, and woody, and occurs in hops, basil, cloves, and cannabis.
Therapeutic qualities and uses include:
Anti-inflammatory (Pichette et al., 2006)
Anti-bacterial (Rogerio et al., 2009)
Anti-tumor (Legault et al., 2003)
Appetite suppressant
Terpinolene
The bouquet of terpinolene is fresh, piney, floral, and herbal. Terpinolene occurs in nutmeg, melaluca (tea tree), conifers, apples, and lilacs.
Therapeutic qualities and uses include:
Anti-bacterial (Akdemir, 2015)
Anticancer (Aydin et al., 2013)
Sedative (Ito and Ito, 2013)
Antioxidant
Combined with THC terpinolene can be uplifting and creative
Terpineol
Terpineol has a floral piney bouquet and occurs in lilacs, pine trees, and eucalyptus. In cannabis, terpineol often occurs in combination with pinene.
Therapeutic qualities and uses include:
Antibiotic (Zengin and Baysal, 2014)
Antioxidant (Bicas et al., 2011)
Anti-tumor (Hassan et al., 2010)
Sedative (Mander and Liu, 2010)
Anti-inflammatory
Anxiolytic
Geraniol
Geraniol is most commonly found in geraniums, which have a fragrance similar to roses. Geraniol also occurs in plants ranging from tobacco to lemons to cannabis.
Therapeutic qualities and uses include:
Antioxidant (Xue et al., 2016)
Anti-tumor/anti-cancer (Lee et al., 2016)
Neuroprotectant (Rekha and Selvakumar, 2013)
Anti-spasmodic (Rekha and Selvakumar, 2013)
Anti-bacterial
Anti-fungal
Anti-viral
Valencene
The bouquet of valencene is citrus—valencia orange, grapefruit, and tangerine with a slight hint of fresh herbs or wood.
Therapeutic qualities and uses include:
Anti-inflammatory (Yang et al., 2016)
Ocimene
Ocimene’s bouquet is described as sweet, herbaceous, and woodsy. It is found in a wide variety of plants including mint, pepper, parsley, mangoes, orchids, and cannabis.
Therapeutic qualities and uses include:
Antifungal
Anti-anxiety