Some science behind the scenes
Tetrahydrocannabinol (THC), is also known as delta-9-tetrahydrocannabinol (Δ9-THC), and Δ1-THC (using an older chemical nomenclature). Δ9-THC is responsible [according to Meyler] for the greater part of the pharmacological effects of cannabis – the primary natural source of THC. Δ8-THC is also active. However the cannabis plant contains more than 400 chemicals, of which some 60 are chemically related to Δ9-THC.
It was first isolated by Yechiel Gaoni and Raphael Mechoulam from the Weizmann Institute of Science in Rehovot, Israel, in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed. An aromatic terpenoid, THC has a very low solubility in water, but good solubility in most organic solvents.
THC, is the only natural substance that binds to the C1 and C2 receptors as an agonist, the rest are natural substances that occur in the body.
At present, there are two known types of cannabinoid receptors, termed CB1 and CB2 with the possibility of more. These receptors are found not just in human beings but in mammals, birds, fish and reptiles. They activate a lot of functions. If I make the rather rash and entirely personal assumption that genes relate to function then the CB2 receptor has over 360 functions [amino acids] whilst the CB1 receptor has 473 functions [amino acids]. This makes it very difficult to talk about the functions activated in any simple way!
The human CB1 and the CB2 receptors share approximately 44% amino acid similarity. When only the transmembrane regions of the receptors are considered, however, the amino acid similarly between the two receptor subtypes is approximately 68%! And when I looked at the descriptions of the two receptors they did indeed seem to share functionality, agonists and antagonists, meaning there was not a lot of point in describing them separately – particularly as research work is so vague on which functions belong to which receptor.
The ‘natural’ agonists are as follows. The only one of real interest is the natural agonist THC :
- Anandamide – occurs in the body, binds to the CB1 and to a lesser extent CB2 receptors
- THC– Tetrahydrocannabinol.
- 2-AG (2-arachidonoyl glycerol) – found in the body, binds to both the CB1 and CB2 receptors
- Virodhamine(O-arachidonoyl ethanolamine – found in the body, this acts as an antagonist of the CB1 receptor and agonist of the CB2 receptor
- Noladin ether (2-arachidonoyl glyceryl ether) – found in the body Noladin binds to the CB1 and CB2 receptors
- NADA(N-arachidonoyl dopamine) – found in the body, it acts as an agonist of the CB1 receptor
- Oleamide is structurally related to anandamide, and has the ability to bind to the CB1 receptor as a full agonist; it occurs naturally in the body. It induces sleep.
Paracetamol is metabolically combined in the body to form AM404, which is a cannaboid reuptake inhibitor, which is why we get pain relief from paracetamol.
There are both natural and synthetic antagonists - MK-9470, SR 141716A, Rimonabant, TM38837, SR147778 (surinabant), AM251, SLV-319 (ibipinabant), Otenabant (CP-945,598), taranabant (MK-0364), SR144528 plus more mostly used in research.
Functions of the agonists
Functionally we know a little of what THC does at the right doses because it mimics the natural substances in our bodies. Thus we do know that THC does one or more of the following:
- Ovulation and making babies, menstrual cycles and bleeding; hormone regulation [some integration between the nervous system and the endocrine system]
- Pain relief, pleasure including orgasmic pleasure - Feelings of bliss, peace, pain relief, sedation and lack of anxiety,
- Appetite and food processing - The processing of food in the liver; actions in our gastrointestinal tract ; appetite – the agonists seem to increase it, the antagonists decrease it; the main action seems to be to help turn fats into energy, presumably if the function isn’t working we get fat and feel worn-out
- Fighting disease - Anti-inflammatory responses; Immune system responses to bacteria; vomiting in response to toxins; fighting the cell proliferation that might lead to cancer
- Cognition and memory
- Temperature control – both raising and lowering the temperature, virodhamine seems to play a special role here
- The sleep wake cycle
- Fluid control – for example the fluid pressure of the ‘aqueous humor’ inside the eye, if this goes wrong we get glaucoma
- Some motor behavior
- Some sensory behaviour