Medical Cannabis
In addition to the most well-known phytocannabinoids THC and CBD, cannabis contains more than 100 other phytocannabinoids.1 The most well-known and commonly-occurring ones include cannabigerol (CBG), beta-caryophyllene (BCP), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC) and tetrahydrocannabivarin (THCV); therapeutic effects have also been proven for these substances (e.g. neuroprotective, anti-inflammatory or modulating properties)2,3,4,5,6,7. These substances (and terpenes) are absent in cannabinoid isolates, however in full-spectrum extracts they are present in varying proportions, which means that a possible entourage effect of the substances can be exploited.
In the future, targeted breeding will help to produce cannabis chemovars with differing phytocannabinoid weighting, depending on the therapeutic requirements or “suitability”.
THC tetrahydrocannabinol (Δ9-THC)
Chemical formula: C21H30O2 Molecular weight: 314.2246 g/mol Boiling point: 157 °CThe best-known cannabinoid is Δ9-tetrahydrocannabinol (Δ9-THC), which was isolated by Yehiel Gaoni and Raphael Mechoulam at the Weizmann Institute of Science in Israel in 1964.1 It is responsible for the renowned ‘high’ and by most people enjoyed psychotropic effects of cannabis. THC amplifies sensory experience (such as hearing, sight, colour perception) and the consumer usually experiences a feeling of general well-being.
The therapeutic potential of cannabis in the treatment of psychiatric disorders is likely based on these effects: Adults with ADHD benefit primarily from an improved concentration, sleep, and impulse control. Similarly often, cannabinoids are used in adults as mood enhancers (antidepressants). THC from cannabis can bring significant relief in various other serious mental illnesses, especially post-traumatic stress disorder (PTSD).
Among the hundreds of cannabinoids contained in the cannabis blossom, Δ9-THC is the most common cannabinoid in most varieties, as the black market has been breeding cannabis mainly for THC-rich genetics in the last decades. In March 2017, THC and THC-containing substances have been classified as prescription drugs within Appendix III of the narcotics law in Germany.
THC increases appetite, which can be exploited for the therapy of cachectic diseases, among others.3 For anorexic patients, THC seems to have at least positive psychological effects.4 THC can – especially in synergy with other phytocannabinoids – stop the growth of certain types of cancer cells, including the much-feared glioblastoma.5,6 Scientifically unconfirmed case reports that can be found on the internet even claim complete remissions.
CBD (cannabidiol)
Chemische Summenformel: C21H30O2
Molekulargewicht: 314,2246 g / mol
Siedepunkt: 157° C
CBD (cannabidiol) is the second most well-known phyto-cannabinoid after THC and generally the second most prevalent phyto-cannabinoid in the cannabis flower.
Unlike THC, CBD is not psychotropic, i.e. it does not evoke euphoria or other altered states of consciousness. CBD even reduces the psychotropic effect of THC.1 It is therefore ideal for the treatment of children, the elderly and patients who prefer to keep their minds clear. CBD is not subject to the Narcotics Act, nevertheless it is a prescription drug when used therapeutically.
CBD predominantly acts as an antipsychotic, anxiolytic, anti-inflammatory, antiemetic, and spasmolytic, and functions partially indirectly through modulation of the THC / CB2 receptor interaction, or by inhibiting the enzymatic degradation of anandamide, an endocannabinoid.
Further mechanisms of actions are recognised for CBD, including agonistic action at the serotonin receptor 5-HT1 and the receptor GPR55, as well as blockage of the μ-opioid receptor.3,4,5
Knowledge regarding the ‘dirty pharmacology’ of CBD continues to grow; a study published in 2018 found that cannabidiol enhances morphine antinociception, reduces NMDA-mediated seizures and reduces stroke damage, all through antagonistic binding to the sigma 1-receptor.6
Terpene
(C5H8)n
Terpenes are further classified by the number of carbons: monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), etc.
Terpenes form the main component of a plant’s essential oils, and over 8,000 different terpenes have been identified to date. They account for the characteristic aroma, taste and the diversity of different flavours in various types of cannabis and wine. Terpenes appear to be important for the precise regulation of cannabis pharmacology.1 It is well-known outside of cannabis research that e.g. the aroma of limonene (a terpene that occurs in cannabis and citrus fruit) is mood-enhancing and pinene (a terpene that occurs in cannabis and conifers) has antiseptic properties.
The medical relevance of terpenes in cannabis
Research regarding the efficacy of terpenes and the role they play in the human organism as well as their synergetic effects with phytocannabinoids is still in its infancy. However, preliminary results indicate that cannabis terpenes do indeed play a significantly greater therapeutic role as initially presumed.2 The interaction of terpenes and cannabinoids, i.e. all active contents of the cannabis plant (“entourage effect”), has not yet been sufficiently let alone dose-dependently researched. What is certain however is that cannabinoid isolates work differently than the full spectrum of the entire bud / plant. This can also explain the different effects various cannabis genetics have: Cannabis varieties and extracts that demonstrate a similar concentration of CBD and THC can nevertheless show different effects due to their variant cannabinoid and terpene profiles – something that could be exploited for differential therapy.
The medically-relevant contribution that terpenes make to the entourage effect lies in a grey area, where almost none of the anecdotal claims have been confirmed in dose-dependent clinical studies. However, scientific hypotheses on the possible effect mechanisms for the anxiety-reducing and sedative effects of some terpenes do exist; most of these involve the GABAa receptor.3,4-17
In addition to the most well-known phytocannabinoids THC and CBD, cannabis contains more than 100 other phytocannabinoids.1 The most well-known and commonly-occurring ones include cannabigerol (CBG), beta-caryophyllene (BCP), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC) and tetrahydrocannabivarin (THCV); therapeutic effects have also been proven for these substances (e.g. neuroprotective, anti-inflammatory or modulating properties)2,3,4,5,6,7. These substances (and terpenes) are absent in cannabinoid isolates, however in full-spectrum extracts they are present in varying proportions, which means that a possible entourage effect of the substances can be exploited.
Cannabigerol CBG
Chemical molecular formula: C21H32O2
Molecular weight: 316,48 g/mol
Boiling point: n.a.
Medicinal effects (experimentally demonstrated)8,3,9,10: anticarcinogenic, anti-inflammatory, appetite-stimulating, antiemetic, intraocular pressure-reducing, analgesic, antibacterial.
Beta-Caryophyllen BCP
Chemical molecular formula: C15H24
Molecular weight: 204,36 g/mol
Boiling point: 260–261 °C
Medicinal effects12: cardioprotective, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antioxidative, anti-inflammatory, antimicrobial and immunomodulating.
Cannabidivarin (CBDV)
Chemical molecular formula: C19H26O2
Molecular weight: 286.41 g/mol
Boiling point: 220° Celsius
Medicinal effects13,14: antiepileptic, antiemetic
The phytocannabinoid cannabidivarin (CBDV) was first identified in the 1970s. Under acidic conditions CBDV isomerises into THCV and in the plant CBDV is the precursor to THCV. Higher concentrations of CBDV and THCV occur more frequently in Cannabis indica than in Cannabis sativa varieties. CBDV appears to demonstrate its medicinal effect at least partially by modulating GABAergic neurotransmission.
Cannabinol CBN
Chemical molecular formula: C21H26O2
Molecular weight: 310.43 g/mol
Boiling point: 185°C
CBN is an oxidation product of THC and unfolds its medicinal effect in a similar way to THC as e.g. an CB1 and CB2 receptor agonist. A high CBN proportion often indicates cannabis that is already older or was subject to higher temperatures. CBN is slightly psychotropic and significantly more sedating than many other known cannabinoids. Cannabis indica varieties in general appear to contain higher CBN amounts than C. sativa ones.
Cannabichromen CBC
Chemical molecular formula: C21H30O2
Molecular weight: 314.47 g/mol
Boiling point: 220°C
Medical effects:2,18,19 antimycotic, antibacterial, anti-inflammatory, anticarcinogenic, anti-depressive, analgesic, promotes neurogenesis.
CBC entfaltet seine medizinische Wirkung ohne Psychotrope Effekte und wirkt bei der Bekämpfung z.B. von Schmerzen, Entzündungen und Depressionen synergetisch mit CBD, THC und/oder CBG zusammen („Entourage Effekt“). Bekannt wurde CBC in den 1980er Jahren vor allem aufgrund seiner Wirksamkeit gegen antibiotika-resistente Krankenhauskeime. Aufgrund seiner positiven synergistischen Effekte enthalten viele neuere medizinische Cannabis-Züchtungen erhöhte Mengen an CBC.
Tetrahydrocannabivarin THCV
Chemical molecular formula: C19H26O2
Molecular weight: 286.41 g/mol
Boiling point: < 220°C
Medical effects20,21,22: appetite-suppressing, regulates blood sugar (type 2 diabetes), neuroprotective, improves motor dysfunction (in animal models for Parkinson’s disease, Alzheimer’s disease)
THCV is an antagonist of CB1 and CB2 receptors in low doses; further effect mechanisms are assumed to exist. The cannabinoid is slightly psychotropic (euphorigenic, energising, anxiety-relieving) and is currently being examined as an effective appetite-suppressant for obesity, among other uses. THCV is being further developed as a potential cannabinoid for the treatment of type 2 diabetics and related metabolic illnesses; the hope is that THCV could be an alternative to the substance Rimonabant, with lesser side effects. Furthermore, the neuroprotective effect and the influence of THCV on motor function offers opportunities for the treatment of neurodegenerative illnesses. In the plant, THCV arises from the precursor cannabidivarin (CBDV). Higher concentrations of CBDV and THCV are found more frequently in Cannabis indica than in Cannabis sativa varieties.