SickMeds Seeds

AlphaCAT and Phytocannabinoids

Cannabis sativa is a plant family with an unique composition: about 400-500 compounds have been detected exclusively in these plants. Among them are approximately 70-80 terpeno-phenol compounds which have collectively been named phytocannabinoids (Izzo et al., 2009; Fisar, 2009) (note: exact numbers differ between reports).

These phytocannabinoids are secondary metabolites of the plant which are recognized by the bodily ECS, inducing the various bodily responses associated with cannabis use (see also Chapter 4 and 5) (Morimoto et al., 2007; Fisar, 2009). These phytocannabinoids should be distinguished from endocannabinoids (which are present in animals) and synthetic cannabinoids (which are fabricated) (Fisar, 2009).

Based on their chemical structure, Elsohly & Slade (2005) divided the different plant cannabinoids into eleven categories (see figure 1). Several well-identified examples of these groups of phytocannabinoids are provided in Figure 4, showing also their chemical structure and effects.

The main constituents of cannabis are, however, delta9-THC and cannabidiol (CBD) (Fisar, 2009). delta9-THC is most well-known for its psychotropic properties, acting upon both the CB1 and CB2 receptor types of the ECS. In both from the cannabinol (CBN) and cannabichromene (CBC) subgroups, compounds are thought to possess delta9-THC-like effects (Fisar, 2009). CBD, on the other hand, is non-psychotropic and has a low affinity for both receptor types, yet displays considerable potency in antagonizing CB1 and CB2 agonists (Fisar, 2009).

CBN-like and cannabigerol-like (CBG) compounds are other non-psychotropic cannabis constituents. Cannabis plants contain also cannabinoid carboxylic acids, which can be transformed to active delta9-THC following heating (Fisar, 2009). As mentioned, there is an extraordinary variety among cannabis plants, both in their chemical and morphological composition, which is dependent on strain, environmental conditions, as well as cultivation methods (Schultes et al., 1975; Clarke & Watson, 2007; UNODC, 2009).

This variety is reflected in variations in the amounts and presence of phytocannabinoids between different plants. Generally speaking, either delta9-THC or CBD is the main constituent and their concentrations in plants is, on average, of 1-12% (Frank & Rosenthal, 1992).

The fact that different cannabis strains and plants differ in their composition is indicated with the term “chemotype”: a specific plant or strain has a certain chemotype with typical quantities of specific phytocannabinoids (Frank & Rosenthal, 1992).

The phytocannabinoids are primarily produced in glandular tissues in the cannabis leaves and stored in sticky droplets, called resin glands. These glands can be found on the surface of all parts of Cannabis sativa, except for roots and seeds (Frank & Rosenthal, 1992).

Generally speaking, resin glands can be divided into three types: bulbous (15-30μm), capitate (25-100µm), and capitate-stalked (150-500μm). The capitate-stalked resin glands are the only ones that can be seen with the naked eye, the rest can be sensed as a sticky layer on top of, for example, the leaves (Frank & Rosenthal, 1992).

The reasons for the unique synthesis and storage of the phytocannabinoids are unknown, but it has been hypothesized that they participate in physiologically relevant events such as pathogen defense (CBD, CBG, and their acids are potent antibiotics) and plant-eating (via their psychotropic actions) (Frank & Rosenthal, 1992; Morimoto et al., 2007). To obtain usable cannabis, the flowers and leaves of the cannabis plant are first dried and then grinded or pressed into a dense mass with a binding agent, yielding yellow or brown hashish (Fisar, 2009).

delta9 - tetrahydrocannabinol

delta9 THC
  • isolated by Gaoni and Mechoulam in 1964
  • primary pscyhotropic ingredient of Cannabis
  • partial agonist at CB1 and CB2
  • mainly used for its palliative effect by inhibiting chemotherapy-induced nausea and vomiting, anti-emetic and apetite booster for AIDS patients, symptomatic relief of neuropathic pain in MS patients, analgesic for cancer patients, euphoric, anti inflammatory
  • delta8 - tetrahydrocannabinol

    delta8 THC
  • product of the isomerization of Δ9-THC, therefore regarded as an artefact
  • concentration in Cannabis is miniscule
  • pharmacology similar to Δ9-THC
  • less expensive and more stable than Δ9-THC, yet not marketed
  • cannabinol

  • isolated by Woods et al. in 1986
  • first natural cannabinoid to be obtained in pure form
  • product of Δ9-THC oxidation, therefore relatively minor consituent in fresh Cannabis but increases when Δ9-THC degrades (e.g. during storage)
  • weak CB1 and CB2 partial agonist (10% of Δ9-THC activity)
  • potential therapeutic application in diseases in which cannabinoid receptors are upregulated
  • sedative, antibiotic, anti-inflammatory, anticonvulsant
  • cannabidiol

  • isolated by Adams et al. in 1940
  • major non-psychotropic cannabinoid
  • multitude of pharmacological effects; evaluated in anxiety, psychosis, movement disorders, analgesic for neuropathic pain in patients with MS, anti-inflammatory and antispasmodic
  • delta9 - tetrahydrocannabivarin

  • isolated by Gil et al. in 1970
  • particularly abundant in Pakistani hashish
  • antagonist of Δ9-THC at low doses
  • agonist of CB1 at higher doses
  • reduces apetite

  • cannabigerol

  • isolated by Gaoni and Mechoulam in 1964
  • nonpsychotropic
  • antiproliferative, antibacterial, antifungal, and anti-inflammatory activity, analgesic
  • potent antagonist of TRPM8 receptor
  • agonist of TRPV1 and TRPA 1 receptors
  • cannabinoid agonist
  • inhibitor of anandamide reuptake

  • cannabidivarin

  • isolated from hasish by Vollner et al. in 1969
  • little is known on its pharmacology and mode of action

  • cannabichromene

  • isolated by Claussen et al. and Gaoni and Mechoulam in 1966
  • non-psychotropic
  • major canniboid in fresh Cannabis (together with Δ9-THC)
  • 2,5 x more toxic than Δ9-THC
  • may cause hypothermia, sedation, and hyperactivity
  • anti-inflammatory, antimicrobial, antifungal and modest analgesic activity
  • potent agonist of TRPA1
  • weak inhibitor of anandamide

  • delta9 - tetrahydrocannabinolic acid

  • two acidic analogs: Δ9-THCA A and Δ9-THCA B
  • Δ9-THCA A isolated by Nishioka et al. in 1967
  • Δ9-THCA B isolated by Mechoulam et al. in 1969
  • potent TRPA1 agonist
  • potent TRPM8 antagonist
  • antiproliferative, antispasmodic, antibacterial and antibiotic activity
  • cannabidiolic acid

  • isolated by Krejci and Santavy in 1955
  • together with CBD, main component of glandular hairs (up to 15%)
  • selective COX-2 inhibitor
  • TRPA1 and TRPV1 agonist
  • TRPM8 antagonist
  • antiproliferative activity
  • Figure 1