Cannabis anandamide

Endocannabinoids. Figure 1 Chemical structures of the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, of Cannabis sativa psychoactive principle, A9-tetrahydrocannabinol, and of the CB-i receptor antagonist/inverse agonist, rimonabant. 

The presence of cannabinoid receptors in the immune system has led to consideration of the effects of cannabis on its function. Cannabinoid receptors have been found in spleen cells (Kaminski et al. 1992). Activation of these receptors would inhibit their function in the immune response. Similar suppressant effects occur on lymphocytes (Diaz et al. 1993). THC and anandamide inhibit macrophage-mediated tumor necrosis (Cabral et al. 1995). Despite these effects, their functional significance remains to be determined. These effects are most likely subtle. 

One such amide present in chocolate is anandamide (N-arachidonoyl-ethanolamine). Anandamide, together with N-oleylethanolamine and N-linoleylethanolamine, bind to a receptor. In the brain which also binds tetrahydrocannabinol, the psychoactive compound in cannabis. Could this explain the addiction ... 

Anandamide inhibited the specific binding of [ H]-HU-243 to synaptosomal membranes in a manner typical of competitive ligands, with an inhibition constant (K ) of 39.0 + 5.0 nM. In this system, the of tsP-THC, a psychoactive compound of cannabis, was 46.0 + 3-0 nM. These were exciting results — the psychoactive compound from a higher plant and a chemically completely different compound in the brain were found to bind to the same brain receptor at about the same level of activity. Soon after the identification of anandamide, this compound was tested for its pharmacological activity. Anandamide administered i.p. in mice, caused... 

Its hypnotic properties were characterized. Its mechanism of action is far from being understood. Although it does not bind with high affinity to CB] or CB2 receptors, it exhibits some cannabimimetic actions, which could be explained at least in part by entourage effects. It is likely that oleamide and anandamide have common as well as distinct pathways of action. The 5-HT2A receptor appears to be a target for oleamide but the possibility of the existence of specific receptors for this compound is still open. Legget et have reported that oleamide is a full cannabi-... 

Cannabis Cannabis sativa Ag-THC Cannabinoid (agonist) Anandamide... 

Some people claim that the effects of low doses of salvinorin are similar to Cannabis and have suggested the possibility that like THC, salvinorin A might bind to the anandamide receptor site (CBl). This site had not been looked at in the NovaScreen study, so in 1998, Siebert submitted a sample of salvinorin A to Dr. Raphael... 

Mechoulam R and Ben-Shabat S (1999) From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol the ongoing story of cannabis. Nat Prod Rep 16, 131-143. 

The high levels recorded in the basal ganglia and cerebellum, regions that coordinate motor functions, strongly suggest that the cannabinoid-anandamide system is involved in this activity. This is supported by the wide spectrum of neurological effects of cannabis or THC in laboratory animals (impaired coordination and balance, decreased muscle tone and reflexes, and, at higher doses, tremor, myoclonic jerks, muscle spasms, and convulsions). In humans, uncoordinated movements, muscle weakness, and tremulousness are frequently observed after cannabis use. 

Cannabis, or marijuana, has been used for centuries for both symptomatic and prophylactic treatment of migraine. It was highly esteemed as a headache remedy by the most prominent physicians of the age between 1874 and 1942, remaining part of the Western pharmacopoeia for this indication even into the mid-20th century. Current ethnobotanical and anecdotal references continue to refer to its efficacy for this malady, and biochemical studies of THC and anandamide have provided a scientific basis for such treatment (Russo, 1998). 

Figure 19.1. Chemical structure of main active ingredient of Cannabis sativa, A9-tetrahydrocannabinol (THC) and the naturally occurring ligand for cannabinoid receptors anandamide (arachidonyl ethanolamide).

Topical application of anandamide to rabbit cerebral arterioles at low concentrations caused a dose-dependent dilation [62]. This observation may be related to the use of cannabis in the past in migraine. 

Cannabinoid receptors include the CB1 receptors (which have a high incidence in the CNS and inhibit adenylyl cyclase, close Ca2+ channels and open K+ channels via Gai) and CB2 receptors (which are present in immune cells and act via Gai proteins to inhibit adenylyl cyclase). CB1 and CB2 receptors bind the endogenous ligand anandamide (arachi-donylethanolamide) as well as A9-tetrahydroc.annabinol from marijuana (Cannabis saliva). A9-Tetrahydroc,annabinol antagonizes the peripheral CB2 receptor but acts as an agonist for the CNS CB1 receptor. Cannabinoid receptor agonists have appetite stimulant and psychoactive effects and have therapeutic potential for relief from nausea and pain. 

Di Marzo V, Breivogel CS, Tao Q, Bridgen DT, Razdan RK, Zimmer AM, Zimmer A, Martin BR (2000b) Levels, metabolism, and pharmacological activity of anandamide in CBi cannabi-noid receptor knockout mice. Evidence for non-CBi, non-CBi receptor-mediated actions of anandamide in mouse brain. J Neurochem 75 2434-2444 Di Marzo V, Melck D, Bisogno T, De Petrocellis L (1998) Endocannabinoids endogenous cannabinoid receptor hgands with neuromodulatory action. Trends Neurosci 21 521-528 Dickinson T, Fleetwood-Walker SM (1999) VIP and PACAP very important in pain Trends Pharmacol Sci 20 324-329... 

Jaggar SI, Hasnie FS, Sellaturay S, Rice ASC (1998) The anti-hyperalgesic actions of the cannabi-noid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain 76 189-199... 

Anandamides can be produced with little investment (eg argon tank, a fatty acid) and yield unlimited quantities. Many of these fatty acid amides are CBl agonists and will replace both THC and cannabis. 

I will not advocate that anyone buy marijuana as it could be unsafe from the street. Buyers clubs offer patients quality control. States that run their own liquor stores could replace buyers clubs. Cannabis could be regulated by the government, fatty acids amides such as anandamide type molecules (CBl agonists) can not be controlled as they can be made from grocery store oils. 

Two subtypes of G protein-coupled receptors for cannabis s psychotropic component, A -tetrahydrocannabinol (THC), have been cloned to date, the cannabinoid CBi and CB2 receptors (Howlett et al. 2004). Yet, five different types of endogenous agonists for these cannabinoid receptors have been identified so far (Fig. 1). These compounds, named endocannabinoids by analogy with THC (Di Marzo and Fontana 1995), are all derived from long-chain polyunsaturated fatty acids. In particular (1) the anandamides are amides of ethanolamine with polyunsaturated fatty acids with at least 20 carbon atoms and three 1,4-diene double bonds. The C20 4 homologue in this series, V-arachidonoylethanolamine (AEA) (Devane et al. 1992), also known simply as anandamide, has been most studied. 

Desarnaud F, Cadas H, Piomelli D (1995) Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization. J Biol Chem 270 6030-6035 Deutsch DG, Chin SA (1993) Enzymatic synthesis and degradation of anandamide, a cannabi-... 

Cannabidiol (CBD) is a non-psychotropic component of cannabis with possible therapeutic use as an anti-inflammatory drug. Recent studies on both enantiomers of CBD showed enantioselectivity in their interaction with cannabinoid and vanniloid (VRl) receptors as well as on the cellular uptake and enzymatic hydrolysis of anandamide (Bisogno et al. 2001). 

McParlland JM, Pruitt P (2002) Sourcing the code searching for the evolutionary origins of cannabinoid receptors, vaniUoid receptors, and anandamide. J Cannabis Ther 2 73-103... 

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