I dont know, but I think, that uses of cannabis must be very carefully practicizied under stricte control. But, from teological views, I dont expert on islamic fate, from ussual reasons (I am only orthodox christian!), and consequently I dont know  is cannabis forbidden or not in islam. Thank you and best vishies in their next work.

Bogdan Nikolić, Belgrade, Serbia, Europe

Cannabis is Hallal. In the book "Hashish: Its Chemistry and Pharmacology" - Ciba Foundation Study Group the 21. of October 1964 - In honour of Professor Dr. G. Joachimoglu 

Natural and smoked Hashish G.Joachimoglu - Department of Pharmacology, University of Athens, and Drug Supervisory Body, United Nations, Geneva.

Fifty years ago, when I was studying medicine at the University of Berlin, I was taught that hashish was used as a pleasure-inducing drug mainly in Eastern countries (especially by Moslems) and that the affects attributed to the drug were different in these people from those observed in Western Europeans. It seems that the wide use of the drug in the East, in contrast to Western Europeans, was connected with this observation.

A relevant statement of the Commission on Narcotic Drugs (1963) reads as follows: "The habitual consumption of cannabis assumes a different character in some industrially developed countries from the one it assumes in countries in which cannabis consumption constitutes a traditional habit practised for hundreds or thousands of years without being subject to any social opprobrium. 

Cannabis users in industrial countries often have a psychopathic personality and the consumption  of cannabis is frequently the first step towards later addiction to heroin or morphine". 

...Discussion (page 12 -13) Extract

... Another interesting aspect  of this was brought out of the Chopras. They have done a great deal of work in India and they point out that in the north among the Moslems of the old  Indian Empire, they smoke hashish more than they do in the south among the Hindus, owing to the fact that they obtain a rather concentrated resinous from Turkestan and the other side of the Himalayas.

- They also point out that a great deal of the potency of the preparation in that part of the world is due to the fact that no seeding is allowed. There are actually special workers, known as cannabis doctors, who go around the fields to make sure that there is no pollination. In Africa, by contrast, you invariably find the seed in cannabis, and yet it produces effects. This is another problem which needs attention 

... Joachimoglu: What you say about India, that they have stronger hashish on one side of the Himalayas than on the other, is obviously true. Digitalis leaves are another example. If you take seeds of digitalis from the garden, you will not get the same amount of glycosides as when it has grow in the forest. The same applies to opium; Dr. Braenden has experience of that. There is a great difference between opium from one country, or one district, and another. I think the same applies to hashish.  

http://www.worldcat.org/title/hashish-its-chemistry-and-pharmacology/oclc/809017336

With best wishes and thank-you

Michael

Hashish: Its Chemistry and Pharmacology (Hashish: Dens Kemi og Farmakologi) - Ciba Foundation Study Group the 21. of October 1964 - In honour of Professor Dr. G. Joachimoglu - In relation

Availability, Potency, Dosage and  Modes of administration as factors (page 60)

... For example Haneveld (1959) draws attention to the fact that in Lebanon fewer than five cannabis "addicts" are admitted to mental hospitals yearly despite the fact that the country is a major producer of the drug for the illegal trade with Egypt. Becker (1953, 1955) agrees that an available supply of cannabis is insufficient per se to lead to habituation and ascribes this to the lack of physical dependence. Adams (1941-42), on the other hand, is of the opinion that the spread of the marihuana habit in the United States of America has been due in part to its ready availability in countless localities, since it grows wild. R.N. and G.S. Chopra (1939) think that ready availability is an important factor in producing the habit.   

 ... In the Indian Peninsula the smoking of charas is prevalent among the Moslems of the North because of its availability in that area, whereas the eating of ganja is commoner among the Hindus of the South because it is there available.

The potency and the dosage of cannabis do not in my opinion matter in determining the production of habit, short of sheer absence of effect. The habitué finds on the basis of average potency a dose which produces the desired effects. Bromberg (1939) points out that any increase in consumption is related to how often the smoker wishes to experience the sensations produced. Increase in dose is rare (I.C. and R.N. Chopra, 1957).

... Smoking is universal in Africa except along North African coastal strip, where some form of oral preparation is de rigueur. Both smoking and eating occur in Morocco (Benabud, 1957). Smoking (charas and ganja) is practised in the Indian Peninsula as well as eating (bhang). Both smoking and eating occur in Mexico but smoking only in the United States of America and Brazil.

The oral method only is used in Greece, Egypt, Syria, Arabia and Persia. Historically, eating of cannabis pre-dates smoking (R.N. and G.S. Chopra, 1939). Details of oral preparations are given by I.C and G.S. Chopra (1957), Adams (1940) and Merrill (1938). ..

... Dependence of cannabis (Page 55)

Is Addition to cannabis a true addiction or a habit? In the view of the Expert Committee of The World Health Organization (1957, 1964) the answer is obviously Habit-forming.

(Smartt 1956) even refers to smoking bhang in Tanganyika as an intoxicant. Asuni (1964) in Nigeria says that cannabis is not a drug of addiction, basing his opinion on the absence of withdrawel symptoms, the absence of necessity for increasing the dose to get the desired effect and "for other resons".

He ascribes apparent "habit to the need for the company of associates (1)", because the habitue has lost fase with "more healthy company". Murphy (1963) has made a valuable review of the literature on "The Cannabis Habit" over the twenty-five years from 1938 to 1963.

He find that the general opinion is that cannabis is habit-forming rather than addiction-producing. The majority of individual users accepted or abandoned the habit without withdrawal symptoms. None showed any tendency to increase the dose. Most, given as much cannabis as they asked for, tended to be quite moderate in their demands, even to reducing the dose.

Marcovitz and Meyers (1944) and Charam and Perelman (1946) investigated two groups consisting mainly of Negro soldiers of the United States Army. These men either demanded a supply of cannabis or they sought discharge from the army on the grounds that they were useless without it.

Murphy's impression was that the individuals concerned "were playing strongly on the nuisance value of there alleged addiction." Charan and Perelman note that "When talked to in a kindly sympathetic manner, feelings of anxiety which they (the sufferers) attributed to the drug deprivation disappeared in the course of the interview, because they were able to represent themselves as adequate individuals in terms of their own standards". 

Murphy observes that this is not the reaction which one would expect from a true addict but rather an attachment to a delinquent sub-culture-on in which marihuana smoking plays a limited but significant role-than a dependency on the drug itself. In neither group were the patients weaned from the drug, which suggests addiction in some form, possibly  to a way of life which cannabis suppots.

Other American observers do not think that cannabis is truly addictive. Allentuck and Bowman (1942) say that "the psychic habituation to marihuana is not as strong as to tobacco or alcohol". Freedman and Rockmore (1946) found no deterioration of mind or body and reported that the most of the users had refrained from using the drug for long periods without reduction in efficiency or need for medical care. 

J.F. Siler (quted by Murphy, 1963) sais in 1933 that in Panama Canal Zone cannabis, as grown there, is not habit-forming "in the sense which the term is applied to alcohol, opium, cocaine, etc." and recommended that no legislative action be taken to prevent the sale or use of marihuana. In 1944 the New York City Mayer's Committee on Marihuana advised that it is neither a significant addiction-producer nor a serious channel of other addictions.

In Morocco (Benabud, 1957) cannabis is not a compulsive need in the country districts but in urban conditions there is "mass addiction". In South Africa, the Medical Staff of the Pretoria Mental Hospital (1938) came to the conclusion that many Africans "used drugs (e.g. cannabis) as the Europeans uses alcohol", only over-indulgence producing marked mental symptoms. I can confirm their opinions (Watt, 1961).

From India, R.N and G.S. Chopra (1939) and I.C. and R.N. Chopra (1957) record similar findings. Haneveld (1959) notes that in Lebanon, where much cannabis is produced for export to Egypt, there is little in way of the cannabis habit despite the easy availability of the drug.

It seems clear therefore that cannabis by itself includes neither dependence nor addiction. Knaffl-Lenz (1952) indicates that it offers an escape from the world and that, for individuals whose personal inadequacy or social misery is great enough, it may led to rejection of life without the drug.

 He observes that this is indistinguishable from addiction. The collective opinion of American observers, according to Bromberg (1939), is that marihuana is not a habit-forming drug. Indeed, he points out that in the Court of General Sessions in New York the difficulty is not to prove that cannabis is narcotic, but that it is habit-forming.

On the basis of ascertainable facts he says that "prolonged use of marihuana constitutes a sensual addiction in that the user wishes to experience again and again the ecstatic sensations and feelings which the drug produces.

Unlike addiction to morphine, which is bio-chemically as well as psychologically determined, prolonged use of marihuana is essentially in the service of the hedonistic elements of the personality". This, I think, puts the position very clearly.

1: "APPARENT HABIT TO THE NEED FOR THE COMPANY OF ASSOCIATES"

Endocannabinoid signaling mediates oxytocin-driven social reward

- Don Wei, et al., Proc Natl Acad Sci U S A. 2015 Nov 10; 112(45): 14084–14089.

Significance

We present evidence that an oxytocin-dependent endocannabinoid signal contributes to the regulation of social reward. The results provide insights into the functions of oxytocin, a neuropeptide crucial for social behavior, and its interactions with other modulatory systems that regulate the rewarding properties of social behavior. They further suggest that oxytocin-driven anandamide signaling may be defective in autism spectrum disorders, and that correcting such deficits might offer a strategy to treat these conditions.

Abstract

Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that SOCIAL CONTACT INCREASES, WHEREAS ISOLATION DECREASES, THE MOBILIZATION OF THE ENDOGENOUS MARIJUANA-LIKE NEUROTRANSMITTER, ANANDAMIDE, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior.

Pharmacological and genetic experiments show that ANANDAMIDE MOBILIZATION AND CONSEQUENT ACTIVATION OF CB1 CANNABINOID RECEPTORS ARE NECESSARY AND SUFFICIENT TO EXPRESS THE REWARDING PROPERTIES OF SOCIAL INTERACTIONS, assessed using a socially conditioned place preference test.

We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc....

The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.

 Human studies have shown that marijuana heightens the saliency of social interactions (1), enhances interpersonal communication (2, 3), and decreases hostile feelings within small social groups (4). The neural mechanisms underlying these prosocial effects are unclear but are likely to involve activation of CB1 cannabinoid receptors, the main molecular target of marijuana in the human brain (5). 

Consistent with this idea, CB1 receptors are highly expressed in associational cortical regions of the frontal lobe and subcortical structures that underpin human social-emotional functioning (6, 7).

Moreover, the receptors and their endogenous lipid-derived ligands, anandamide and 2-arachidonoyl-sn-glycerol (2-AG) (8), have been implicated in the control of social play (9) and social anxiety (10, 11), two crucial aspects of the social experience.

Another essential facet of social behavior, the adaptive reinforcement of interactions among members of a group (i.e., the reward of being social), requires the oxytocin-dependent induction of long-term synaptic plasticity at excitatory synapses of the nucleus accumbens (NAc) (12), a key region in the brain reward circuit.

Because the endocannabinoid system regulates the reinforcement of various natural stimuli (13) as well as NAc neurotransmission (14), in the present study we tested the hypothesis that this signaling complex might cooperate with oxytocin to control social reward.

... The results suggest that social contact stimulates anandamide mobilization in NAc and vHC, two regions of the mouse brain that are involved in the control of motivated behavior. Importantly, one of these regions, the NAc, has been recently implicated in the regulation of social reward by the hypothalamic neuropeptide oxytocin (12).

… In conclusion, our results illuminate a mechanism underlying the prosocial actions of oxytocin, and PROVIDE UNEXPECTED INSIGHTS ON POSSIBLE NEURAL SUBSTRATES INVOLVED IN THE SOCIAL FACILITATION CAUSED BY MARIJUANA. Pharmacological modulation of oxytocin-driven anandamide signaling (by using, for example, FAAH inhibitors(and/or marijuana/phytocannabinoids) might open new avenues to treat social impairment in autism spectrum disorders (and/or personal loneliness). 

- Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697;

- Department of Pharmacology, School of Medicine, University of the Basque Country, Barrio Sarriena s/n, Leioa 48940, Spain; and ...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653148/

http://www.worldcat.org/title/hashish-its-chemistry-and-pharmacology/oclc/809017336

"Rejection of life without the drug/cannabis".

High on Life? Medical Marijuana Laws and Suicide

D. Mark Anderson, et al, The Institute for the Study of Labor (IZA) - Discussion Paper Series IZA DP No. 6280, January 2012

 ABSTRACT

Using state-level data for the period 1990 through 2007, we estimate the effect of legalizing medical marijuana on suicide rates. Our results suggest that the passage of a medical marijuana law is associated with an almost 5 percent reduction in the total suicide rate, an 11 percent reduction in the suicide rate of 20- through 29-year-old males, and a 9 percent reduction in the suicide rate of 30- through 39-year-old males. Estimates of the relationship between legalization and female suicides are less precise and are sensitive to functional form.

- D. Mark Anderson Montana State University, Daniel I. Rees University of Colorado Denver and IZA, Joseph J. Sabia San Diego State University

http://ftp.iza.org/dp6280.pdf

Effect of Cannabinoid Receptor Activation on Spreading Depression

Hadi Kazemi, et al., Iran J Basic Med Sci. 2012 Jul-Aug; 15(4): 926–936. 

Abstract

Objective(s): The objective of this study was to evaluate the effect of cannabinoid on cortical spreading depression (CSD) in rat brain. Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine. CSD is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain.

Materials and Methods: The effects of Delta9-tetrahydrocannabinol (THC), as well as, cannabinoid CB1 and CB2 receptor agonists on CSD in rat neocortical slices were investigated. Furthermore, the effect of cannabinoid CB1 agonist was tested on field excitatory postsynaptic potentials (fEPSP) and long-term potentiation (LTP).

Results: HC (1-20 microM) dose dependently suppressed CSD amplitude, duration, and propagation velocity. Cannabinoid CB1 agonist, WIN 55,212-2 mesylate (1-10 microM), also significantly suppressed all characteristic features of CSD. However, cannabinoid CB2 agonist, JWH-133 (1-20 microM), did not affect CSD. FEPSP and induction of LTP were suppressed by application of WIN55212-2.

Conclusion: Suppression of CSD by activation of CB1 receptors points to the potential therapeutic effects of cannabinoids in migraine with aura. More research is needed before we know whether cannabinoids may be helpful in treating migraine pain.

- Shefa Neuroscience Research Centre, Tehran, Iran

- Department of Pediatrics, Shahed University, Tehran, Iran

- Institut für Physiologie I, Westfalische Wilhelms-Universitat Munster, Münster, Germany

Endocannabinoids in chronic migraine: CSF findings suggest a system failure.

Sarchielli P, et al, Neuropsychopharmacology. 2007 Jun;32(6):1384-90.

Based on experimental evidence of the antinociceptive action of endocannabinoids and their role in the modulation of trigeminovascular system activation, we hypothesized that the endocannabinoid system may be dysfunctional in chronic migraine (CM).

We examined whether the concentrations of N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and 2-arakidonoyl-glycerol (2-AG) in the CSF of patients with CM and with probable CM and probable analgesic-overuse headache (PCM+PAOH) are altered compared with control subjects.

... CSF concentrations of AEA were significantly lower and those of PEA slightly but significantly higher both in patients with CM and PCM+PAOH than in nonmigraineur controls (p

Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

Marcus A. Bachhuber, MD, et al., JAMA Intern Med. 2014 Oct; 174(10): 1668–1673.

Abstract

IMPORTANCE

Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.

OBJECTIVE

To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.

DESIGN, SETTING, AND PARTICIPANTS

A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included.

EXPOSURES

Presence of a law establishing a medical cannabis program in the state.

MAIN OUTCOMES AND MEASURES

Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate.

RESULTS

Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws.

Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar.

CONCLUSIONS AND RELEVANCE

Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.

- Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania (Bachhuber) and ...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392651/

http://miami.cbslocal.com/2017/05/01/medical-cannabis-marijuana-cure-opioid-epidemic/

CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats.

Navarro M, et al., Neuroreport. 1998 Oct 26;9(15):3397-402.

Recent reports have provided evidence of a link between the endogenous brain cannabinoid system and the endogenous central opioid systems. Here we report that the selective CB1 receptor antagonist SR 141716A induced behavioral and endocrine alterations associated with opiate withdrawal in morphine-dependent animals in a dose-dependent manner and that naloxone induced an opiate withdrawal syndrome in animals made cannabinoid-dependent by repeated administration of the potent cannabinoid agonist HU-210.

Additionally CB1 and mu-opioid receptor mRNAs were co-localized in brain areas relevant for opiate withdrawal such as the nucleus accumbens, septum, dorsal striatum, the central amygdaloid nucleus and the habenular complex.

These results suggest that CB1 cannabinoid receptors may play a role in the neuroadaptive processes associated with opiate dependence, and they lend further support for the hypothesis of a potential role of cannabinoid receptors in the neurobiological changes that culminate in drug addiction.

- Instituto Universitario de Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Spain.

* CB1 cannabinoid receptor antagonist-induced opiate withdrawal

Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin (THCV) is a cannabinoid CB1 and CB2 receptor antagonist.

Thomas A, et al., Br J Pharmacol. 2005 Dec;146(7):917-26.

Abstract

Delta9-tetrahydrocannabivarin (THCV) displaced [(3)H]CP55940 from specific binding sites on mouse brain and CHO-hCB(2) cell membranes (K(i)=75.4 and 62.8 nM, respectively).

THCV (1 microM) also antagonized CP55940-induced stimulation of [(35)S]GTPgammaS binding to these membranes (apparent K(B)=93.1 and 10.1 nM, respectively).

In the mouse vas deferens, the ability of Delta9-tetrahydrocannabinol (THC) to inhibit electrically evoked contractions was antagonized by THCV, its apparent K(B)-value (96.7 nM) approximating the apparent K(B)-values for its antagonism of CP55940- and R-(+)-WIN55212-induced stimulation of [(35)S]GTPgammaS binding to mouse brain membranes. ...

In conclusion, THCV behaves as a competitive CB(1) and CB(2) receptor antagonist. In the vas deferens, it antagonized several cannabinoids more potently than THC and was also more potent against CP55940 and R-(+)-WIN55212 in this tissue than in brain membranes. The bases of these agonist- and tissue-dependent effects remain to be established.

- School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD

Are cannabidiol and Δ9-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review

John M McPartland, et al., Br J Pharmacol. 2015 Feb; 172(3): 737–753. 

Based upon evidence that the therapeutic properties of Cannabis preparations are not solely dependent upon the presence of Δ9-tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV).

Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant.

Here, we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta-analysis. Synthesized data regarding mechanisms are then used to interpret results from recent pre-clinical animal studies and clinical trials.

The evidence indicates that CBD and THCV are not rimonabant-like in their action and thus appear very unlikely to produce unwanted CNS effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors:

CBD is a very low-affinity CB1 ligand that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.

These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.

- Division of Molecular Biology, GW Pharmaceuticals, Salisbury, Wiltshire, UK

*  Delta9-tetrahydrocannabivarin (THCV: C19H26O2; n4) Plants with elevated levels of propyl cannabinoids (including THCV) have been found in populations of Cannabis sativa L. ssp. indica (= Cannabis indica Lam.) from China, India, Nepal, Thailand, Afghanistan, and Pakistan, as well as southern and western Africa. THCV levels up to 53.7% of total cannabinoids have been reported. (wikipedia)

* n4-fatty acid: … Omega-4 fatty acids are also important in cell membrane composition. Their increased presence in membranes increases for instance fluidity and protection to salt stress and freezing. Moreover, increased unsaturation is beneficial in processes such as protein sorting mediated by lipid rafts in the membrane. This improves the cell functionality and increases the protection of the cell against cellular damages. Further, omega-4 fatty acids have anti-oxidative properties, anti-tumor promoting and anti-inflammatory protective activities after cell damage (against possible pathogens).... Composition comprising omega-7 and/or omega-4 fatty acids

* n-3 PUFAs have beneficial health effects which are believed to be partly related to their anti-inflammatory properties, however the exact mechanisms behind this are unknown. One possible explanation could be via their conversion to N-acyl ethanolamines (NAEs), which are known to possess anti-inflammatory properties.

Using fatty acid precursors we showed that 3T3-L1 adipocytes are indeed able to convert docosahexaenoic acid (DHA: C22H32O2) and eicosapentaenoic acid (EPA: C20H30O2) to their NAE derivatives docosahexaenoyl ethanolamine (DHEA: anandamid (22:6, n-3): C24H37NO2) and eicosapentaenoyl ethanolamine (EPEA; anandamid (20:5, n-3): C22H35NO2), respectively. ...

Results of combined incubations with PPAR-gamma and CB2 antagonists suggest a role of these receptors in mediating the reduction of IL-6 by DHEA. Our results are in line with the hypothesis that in addition to other pathways, formation of N-acyl ethanolamines may contribute to the biological activity of n-3 PUFAs. Different targets, including the endocannabinoid system, may be involved in the immune-modulating activity of these "fish-oil-derived NAEs." - Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties.

https://www.ncbi.nlm.nih.gov/pubmed/9855288

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751228/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301686/

https://en.wikipedia.org/wiki/Tetrahydrocannabivarin

http://www.google.com/patents/WO2010149662A1?cl=en

https://www.ncbi.nlm.nih.gov/pubmed/20601112

The medical use of cannabis is forbidden (Haram) if the Halal alternative is available. It may be used only when necessary, i.e. when the Halal alternative is not available.

The Messenger of Allah (peace and blessings of Allah be upon him) said: "Allah has not made healing my nation in what is forbidden (Haram) to them."

"Cannabis is forbidden (Haram) if the Halal alternative is available." What is the alternative to cannabis/cannabinoids, endocannabinoids and the endocannabinoid system? Plants came before animals, also with an endocannabinoid system (1), like the later evolution made animals -> humans.

Targeted metabolomics shows plasticity in the evolution of signaling lipids and uncovers old and new endocannabinoids in the plant kingdom

María Salomé Gachet, et al, Sci Rep. 2017; 7: 41177. 

The remarkable absence of arachidonic acid (AA: C20H32O2; 20:4,n6) in seed plants prompted us to systematically study the presence of C20 polyunsaturated fatty acids, stearic acid, oleic acid, jasmonic acid (JA: C12H18O3), N-acylethanolamines (NAEs) and endocannabinoids (ECs) in 71 plant species representative of major phylogenetic clades.

Given the difficulty of extrapolating information about lipid metabolites from genetic data we employed targeted metabolomics using LC-MS/MS and GC-MS to study these signaling lipids in plant evolution.

Intriguingly, the distribution of AA among the clades showed an inverse correlation with JA which was less present in algae, bryophytes and monilophytes.

Conversely, ECs co-occurred with AA in algae and in the lower plants (bryophytes and monilophytes), thus prior to the evolution of cannabinoid receptors in Animalia.

We identified two novel EC-like molecules derived from the eicosatetraenoic acid juniperonic acid, an omega-3 structural isomer of AA, namely juniperoyl ethanolamide and 2-juniperoyl glycerol in gymnosperms, lycophytes and few monilophytes.

Principal component analysis of the targeted metabolic profiles suggested that distinct NAEs may occur in different monophyletic taxa.

This is the first report on the molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicating biosynthetic plasticity and potential physiological roles of EC-like lipids in plants.

- Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland

- School of Pharmaceutical Science, University of Geneva, University of Lausanne, 1 rue Michel Servet, 1211 Geneva 4, Switzerland

Polyunsaturates and Endocannabinoids

Arachidonic acid (AA: C20H32O2; 20:4,n6) -> AEA and 2-AG

Anandamide (AEA: C22H37NO2; 20:4,n6)

2-Arachidonoylglycerol (2-AG: C23H38O4; 20:4,n6)

Phytocannabinoids (polyunsaturates; n6) and metabolism in plants and humans:

* → 9-Carboxy-Delta(9)-thc (-COOH): THCA/CBDA: C22H30O4 → Intense heating/storage: decarboxylation (> 180°C → 200°C) → THC/CBD (C21H30O2) Oxidation → THC -OH (hydroxy: C21H30O3) oxidation and carboxylation and fatty acid desaturase → 11-nor-9-carboxy-delta(9)-THC/THC-COOH: C21H28O4) →

The Brain's Own Marijuana, Scientific America, December 2004:

Endocannabinoid signaling at the periphery: 50 years after THC.

Maccarrone M, et al., Trends Pharmacol Sci. 2015 May;36(5):277-96. 

In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize, and degrade them and that together form the eCB system (ECS).

eCBs control basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation.

Unsurprisingly, in the past two decades eCBs have been recognized as key mediators of several aspects of human pathophysiology and thus have emerged to be among the most widespread and versatile signaling molecules ever discovered.

Here some of the pioneers of this research field review the state of the art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.

- Center of Integrated Research, Campus Bio-Medico University, Rome, Italy; Center for Brain Research, Santa Lucia Foundation IRCCS, Rome, Italy. - and other

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264637/

https://www.nature.com/articles/srep41177/figures/3

http://media.avvosites.com/upload/sites/2029/2016/07/BrainsOwnMJ-SA04-NoPix.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420685/

A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice

Andras Bilkei-Gorzo, et al., Nature Medicine (2017) doi:10.1038/nm.4311 - 08 May 2017

The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging.

The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG: C23H38O4; 20:4, n6) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated.

Here we show that a low dose of Δ9-tetrahydrocannabinol (THC: C21H30O2) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density.

THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months.

The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.

-  Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.

A chronic low dose of Δ9-tetrahydrocannabinol (THC): THC-COOH:

* → 9-Carboxy-Delta(9)-thc (-COOH): THCA: C22H30O4 → Intense heating/storage: decarboxylation (> 180°C → 200°C) → THC (C21H30O2) Oxidation → THC -OH (hydroxy: C21H30O3) oxidation and carboxylation and fatty acid desaturase → 11-nor-9-carboxy-delta(9)-THC/THC-COOH: C21H28O4) → (2-AG: C23H38O4; 20:4, n6)

https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4311.html

Folk Methodology of Charas (Hashish) Production and Its Marketing at Afridi Tirah, Federally Administered Tribal Areas (FATA), Pakistan

Muhammad Hamayun, et al., Journal of Industrial Hemp Volume 9, 2004 - Issue 2

Afridi Tirah is one of the most remote areas of Pakistan bordering Afghanistan. It is a semi-autonomous region, surrounded by lofty mountains. The inhabitants belong to the Afridi tribe of Pathans. They follow their own customs in every sphere of life and discourage any outside interference so much that even the pertinent Political Agent hesitates to visit the valley.

Cannabis sativa L. has been cultivated in the area for hundreds of years. Charas (hashish) is produced in large quantities from Cannabis through folk means. The resinous bract around the seed gives the most potent and best quality drug. The quality of drug deteriorates with increasing percentage of adulterants and contaminants like leaves and small twigs. The charas (“black gold”) produced is not only used locally, but also smuggled to other parts of Pakistan and abroad. In Afridi Tirah, more than 75% of the men above the age of 15 are habitual charas users. Amongst women, this percentage is negligible due to the traditional limitations of local custom.

- Government Degree College , NWFP, Kotha, Swabi, Pakistan & Zabta Khan Shinwari

Pages 41-50 | Received 30 Jun 2003, Accepted 01 Dec 2003, Published online: 25 Sep 2008

Article Folk Methodology of Charas (Hashish) Production and Its Mark...