1. Cannabis
Prof. Suleiman Olimat

2. Cannabis
القنب الهندي
نبات الحشيش

3. Cannabis is a genus of flowering plant that includes one or more species. The plant is believed to have originated in the mountainous regions just north-west of the Himalayas in India, though it could also have come from Northern Africa. It is also known as hemp, although this term usually refers to Cannabis cultivated for non-drug use.

4. Cannabis spp. There are three species known:
Cannabis sativa, C. indica and C. rudelaris
The leaves are the most recognisable and well-known aspect of the cannabis plant. Despite the great degree of variation found naturally in local populations of cannabis, the leaves do not alter greatly in appearance between varieties.

7. Hemp

8. What is Marijuana?
Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant.
Hashish is the resin, or sap, harvested from the plant.
Hashish oil is the essential oil of the female Cannabis Sativa plant.

9. Marijuana – History of Use
Cannabis – native to central Asia
Chinese – first to use, employed for fabric, medicines
India – country where first used for hallucinogenic properties
Africa – introduced through Arab traders; used as medicine
Europe – became popular in 1800s
U.S.A. – 1900s -- use proscribed, outlawed
End of 20th century – contentious debate regarding merits of legalization

10. HempvsMarijuana-1
The word "hemp"is English for a number of varieties of the Cannabisplant, particularly the varieties like "industrial hemp" that were bred over time for industrial uses such as fuel, fiber, paper, seed, food, oil, etc

11. HempvsMarijuana-2
The term "marijuana"is of Spanish derivation, and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes, like Cannabisindica, and certain strains of Cannabissativa.

12. HempvsMarijuana-3 Two cannabinoids are preponderant in Cannabis
THC CBD
psychoactive ingredient antipsychoactive ingredient Marijuana Hemp
(leaves and flowers of the female plant)
High in THC High in CBD
Low in THC
Low in CBD

13. Cannabis Biology
Major Drug Component – delta-trans-tetrahydrocannabinol (THC)
binds to specific receptors in brain
THC- produced in glands on leaves and flowers
-- female plants produce more glands
-- gland production stimulated by heat, sunlight, drought
-- sinsemilla (sin = without semilla = seeds) – particularly strong
Hashish – product - relatively pure resin
The major drug component is produced in small, subsessile glands on the surfaces of leaves, stems, and other parts. The density of glands varies greatly between different parts of the plant, between plants grown in different environments, and between different cultivated lines. For instance, glands may be almost entirely absent from fiber plants.
Glands
THC 13

14. Chemical constituents of Cannabis
Cannabinoids (66)
Nitrogenous compounds (27)
Amino acids(18)
Proteins/ enzymes (11)
Sugars (34)
Hydrocarbons (50)
Simple alcohols (7)
Simple aldehydes (12)
Simple ketones (13)
Simple acids (21)
Fatty acids (22)
Simple esters/lactones (13)
Steroids (11)
Terpenes (20)
Non-cannabinoid phenols (25)
Flavoroids (21)
Vitamins (1)
Pigments (2)
Elements (9)
Total known compounds (483)

15. What is a cannabinoid?
Initially, compounds extracted by Cannabis spp producing characteristic psychoactivity
Later, compounds with a characteristic terpenoid structure
Currently, most any compound that produces cannabinoid psychoactivity, natural or synthetic
Occasionally, just compounds that will interact with cannabinoid receptors
Varying definitions 15

16. What are cannabinoids?
Group of >60 dibenzopyran chemicals found in leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)
Some common cannabinoids are:
In the plant:
In your body (endogenous):
Synthetic
Δ9 – THC
2-arichidonyl glycerol (2 – AG)
CP 55,940
Δ8 – THC
anandamide
HU – 210
cannabidiol and cannabinol

17. Natural cannabinoids
Various structures, most only a few interact with known receptors 17

19. Representative cannabinoids
Classical cannabinoids
Non-classical cannabinoid
Aminoalkylindole
CB1 antagonists 19

20. Endogenous cannabinoids
Receptors suggest endogenous ligands
Two main families identified
Both arachidonic acid derivatives
Precursors in membranes
“Made on demand”
Amides (anandamide)
Esters (2-AG)
Significant differences
Routes of synthesis
Mode of degradation (FAAH vs MAGL)
Efficacy 20

21. Endocannabinoids
Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid. It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body). It is about as potent as THC

22. Structure of THC and synthetic analogs
Most potent analog: 100s times more potent than THC
Lipophilic side chain
Go through this slide to show the students first delta 9 THC - point out their dibenzopyran structure and there long carbon side chains explaining their lipophilicity.
Then show the endogenous cannabinoids
Anandamide - ananda is the sanskrit word for bliss - amide describes the amide linkage in anandamide.
2-AG or 2 arachidonyl glycerol
Both these are eicosanoids that is they are arachidonic acid derivatives
Then point out the synthetics CP 55,940 (30 times as potent as THC - lacks the central pyran ring) and HU -210 the most potent cannabinoid known to humankind(about times as potent as THC (tell anecdote of rumours of a Professor who tried it and remained cataleptic (could not move) in his office for 48 hours.

24. with
4 major cannabinoids in the plant:
2 isomers, a trans-delta-9-THC and a delta-8-THC
A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)
A cannabinol a decomposition product of THC that accumulates as cannabis samples age.
After ingestion, delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active.

25. THC 1,1’-di-methyl-pyrane ring (B ring)
Variedly aromatic ring (C Ring)
Variedly unsaturated cyclohexyl ring (A ring)

26. Results of SAR Psychoactive properties are (-) trans-enatioselective
Length, lipophilicity C3 alkyl chain
Phenolic hydroxyl-group
C9 substitute

27. Modes of Absorption
The most common method of absorption is smoking. Either in a loosely rolled cigarette called a joint, or through a pipe or water pipe.

28. Smoking and the Body THC enters the body through the Lungs.
The smoke is inhaled and held in the lungs.
All affect how much THC will enter the plasma
THC crosses the blood barrier through the capillaries in the lungs
After inhalation THC can reach the brain in about 14 seconds

30. Most THC is absorbed from the blood within 30 min.
After a 6 min smoking period, peak blood levels reached at about 7 min (100 ng/ml plasma).
Most THC is absorbed from the blood within 30 min.
Moves rapidly into the brain and across the blood/brain/placental barrier. Because fatty chains make it very lipid soluble.
Half-life is about 19 hours. Can store in fat cells.
Established physiological effects are dose related.
Lethal dose for THC use has now been studied, and no human deaths have been reported due to intoxication from cannabis.
Lethal dose would be about 1000 x the dose needed for intoxication and used for recreation

31. Metabolites
Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use.

32. 2/3 of metabolites are excreted in feces.
Primary metabolite has a half-life of 50 hours. The complete elimination of the drug can take as long as 6 weeks!
After ingestion, delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active.
2/3 of metabolites are excreted in feces.
1/3 of metabolites are excreted in urine.
Bile = lipid soluble. Most drugs are excreted in the urine.
Urine inactivates metabolites because of it’s acidity. So, in this case, drinking the urine of a user wouldn’t work.

34. Cannabis Pharmacology
Primary Cannabinoids from Cannabis are:
Cannabinol (CBN), Cannabidiol (CBD) and Tetrahydrocannabinol (THC)
THC (D-9-THC ) is the only one with significant psychoactive properties
CBN - 1/10 th activity of THC; CBD - none

35. 2 isomers, a trans-delta-9-THC and a delta-8-THC
A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)
A cannabinol a decomposition product of THC that accumulates as cannabis samples age.
After ingestion, delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active.

36. Therapeutic Antiemetic Reduction of intra-ocular tension Analgesic
Muscle relaxant
Anti-convulsant
Anti-inflammatory
appetite: “the munchies”.
It is one of the most well-known effects of marijuana: the powerful surge in appetite many users feel after smoking or ingesting the drug, colloquially known as "the munchies.

37. Marinol
THC in a sesame oil suspension

38. Cannabinoid Receptors
Beforethe 1980s, it was often speculated that cannabinoids produced their effects through non specific interaction with cell membranes, instead of interacting with specific receptors.
The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals, and have been found in mammals, birds, fishes, and reptiles.
There are currently two known types of cannabinoid receptors, CB1 and CB2.

39. CB1 Receptors
Found primarily in the brain (specifically basal ganglia, limbic system, including the hippocampus, and cerebellum)
􀂾Most dense in brain regions involved with thinking and memory, attention and control of movement􀂾
Also present in both male and female reproductive systems as well as in the lungs, liver and kidneys
􀂾Appear to be responsible for the euphoric and anticonvulsive effects of Cannabis
􀂾Essentially absent in the medulla oblongata, the part of the brain that is responsible for respiratory and cardiovascular functions.
Thus, there is no risk of respiratory or cardiovascular failure as there is with many other drugs.

40. CB2 Receptor
CB2 receptors are almost exclusively found in the immune system (T cells, macrophages, B cells), with the greatest density in the spleen
􀂾CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis
􀂾Also expressed on peripheral nerve terminals

41. Cannabis and Δ9- (THC) for weight loss?
Obesity is one of the highest preventable causes of morbidity and mortality in the developed world. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the 'munchies'). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile.

42. What is obesity ?

43. Obesity is characterized by an abnormal accumulation of body fat, usually 20 percent or more over an individual's ideal body weight. Obesity results when the size or number of fat cells in a person's body increases. When a person gains weight, these fat cells first increase in size and later in number. When a person starts losing weight, the cells decreas ein size, but their number generally stays the same. This is part of the reason that once you gain a significant amount of weight, it is more difficult to lose it.

44. The clinical definition of obesity is a body mass index(BMI)of 30 or higher.
BMI = Weight (in kg) / Height (in meters) Squared

45. Rimonabant Acomplia®(Sanofi-Aventis) launched in Europe in 2006 for
oral treatment of obesity at 20 mg
once daily
Selective blocker of central
and peripheral CB1 receptors,
It reduces food intake and improves lipid and glucose metabolism

47. Rimonabant

48. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market.