The document discusses the history, functions, and effects of cannabinoids as they interact with the body's cannabinoid receptors, notably CB1 and CB2. It details their role in various physiological processes such as pain perception, appetite regulation, and anxiety, along with the implications of cannabinoid use in psychiatric conditions and other health issues. The document highlights potential therapeutic applications, including the use of synthetic THC for nausea in chemotherapy and the challenges posed by cannabinoid-related psychosis.

1. Dr.Samin Sameed
Psychiatrist, KIMS HOSPITAL KOCHI,Kerala
contact- 9743474568

2.  Cannabinoids are a group of chemicals which activate
the body’s cannabinoid receptors.
Endogenous Herbal Synthetic

3. History
 Medicinal use of Cannabis
described by Chinese
emperor Shen Nung (2700BC)

4.  1899- Cannabinol isolated from
cannabis resin
 1964- discovery of structure of D9-
THC
 1990- brain cannabinoid receptor, CB1.
 1992- Anandamide
 1994- CB2

5.  1994- Rimonabant –CB1 blocker.
 1995- 2-AG
 1996- FAAH discovered.

6. Raphael Mechoulam and Yeheel
Gaoni
Raphael Mechoulam

7. Getting high!
 Cannabis acting on a neural pathway involving
cannabinoids endogenous to the human brain
ENDOCANNABINOIDS

8.  THC acid is the
predominant form of the
plant THC, and this is
readily converted to THC
upon heating, such as
when cannabis is smoked.
 Estimates suggest that 20
to 80 µg of THC reach the
brain after one smokes a
marijuana cigarette

9. Endocannabinoids

10. Anandamide
 Mimic THC
 Inhibition of spontaneous movement
 Reduces pain sensitivity
 Decreases body temperature.

11. Others
 2-arachidonylglycerol (2-AG)
 N-arachidonyldopamine (NADA)
 2-arachidonoyl glycerol ether (noladin ether),
 Virodhamine

13. Bio synthesis
 Arachidonic acid -building block
 Endocannabinoids are not stored in synaptic vesicles for
later use, but are synthesized on demand
 Endocannabinoids are highly lipophilic and thus poorly
soluble in cerebrospinal fluid (CSF)

14.  Converts anandamide to arachidonic acid and
ethanolamine
 Found in regions of the brain where CB1 receptors are
predominant
 Inhibitors of FAAH -analgesic effects and reduce anxiety in
animal models,

15. Cannabinoid receptors
 CB1 receptors
 axons and nerve termini, with little present on neuronal
dendrites and the cell body.
 presynaptic rather than postsynaptic side of the neuronal
cleft .
 CB2 - expressed on the surface of white blood cells of the
immune system,

16. Cannabinoid mechanisms

17. Neurotransmission
 G proteins intracellular signaling  inhibition
of adenylyl cyclase  decrease in cyclic
adenosine monophosphate.
 Activation of potassium channels
 Inhibition of N-type calcium channels
 Block the release of a variety of neurotransmitters-
GABA, nor epinephrine, and acetylcholine.

18.  Increase the release of brain endorphin neurotransmitters
 Increase dopamine release in the nucleus accumbens
 Synaptic plasticity, including LTP and long-term
depression (LTD).

19. 
Endocannabinoids may be
the best retrograde
messenger that diffuses from
a postsynaptic neuron to act
upon a presynaptic neuron

20.  Endocannabinoid-mediated inhibition of
neurotransmission Transient and long lasting.
 Transient,also termed DSI(depolarization-induced
Suppression of inhibition) or DSE(depolarization-
induced suppression of excitation),

22. Anxiety and Mood
 Tranquillizing effect
 Loss of signaling by the
endocannabinoid system appears
to promote anxiety-like states.
 Anandamide and 2-AG were
found to increase in the
amygdala immediately following
exposure of mice to stress

23.  Enhancing levels of endocannabinoids may represent a
therapeutic target for anxiety
 Novel FAAH inhibitors reduce anxiety-like behaviors
 Cannabinoid interacts with 5HT1A receptors and this
interaction seems to be involved in its anxiolytic-like
effects

24. CB1 Antagonist-Rimonabant
 Rimonabant - SR141716 or
acomplia, first cb1antagonist
reported.
 Primary indication - Obesity
 Secondary indications -improves
dyslipidemia and improves
glucose homeostasis.
 Long term use increase suicidal
ideation

25.  CB1 receptor activation enhance alcohol consumption while
blocking these receptors decreases consumption
 The usefulness of CB1 antagonism in smoking cessation has
been investigated in the STRATUS-US trial

26. Addiction
 Mice deficient in CB1 receptors - resistant
to the behavioral effects of cannabinoids
 Increase the release of dopamine in the
nucleus accumbens,
 Rats with a preference to alcohol have
decreased FAAH activity

27. Psychosis
 Cannabis use -worsens psychosis in schizophrenia,
 Heavy use –schizophrenia
 Increase the release of dopamine
 Elevated levels of anandamide in CSF.
 Elevated CB1 receptor levels in postmortem brain -
dorsolateral prefrontal cortex and cingulate cortex

28. Feeding
 Increased appetite – “munchies”
 Depend on CB1 receptors
present in the hypothalamus
 CB1 receptor antagonist,
rimonabant, appears to
facilitate weight loss by blocking
cannabinoid signaling.

29. Brain Injury and Pain
 2-AG appears neuroprotective, reducing
brain edema, infarct size, and cell
death, while improving functional
outcomes.
 Regulate pain perception
 FAAH inhibitors improved motor
symptoms in a mouse model of
Parkinson's disease

30.  CB1 receptor plays an important role in these effects
as the analgesic effects of cannabinoid drugs are lost
when CB1 antagonist rimonabant is given
 Mediate stress-induced analgesia

31. Alzheimer’s disease
 Analysis of postmortem brains
from patients with AD-
Upregulation of CB2
receptors
endocannabinoid-degrading
enzyme,
fatty acid amide hydrolase
(FAAH) in glial cells
associated with senile Plaques.

32.  Direct relaxation of vascular smooth muscle
by local CB1 receptors.
 Conjunctiva of the eyes - “bloodshot”
appearance in some cannabis users.
 Relaxation of ocular arteries - treatment for
glaucoma

33.  Synthetic 9 THC Dronabinol is approved in the US for
treatment of nausea and vomiting associated with
chemotherapy as well as an appetite stimulate in AIDS.

34. References
 108-115:James Sadock,Viginia Alcott Sadock.
Comprehensive text book of psychiatrty.
 10.1192/bjp.178.2.116 Published 1 February 2001
 Pharmacol Rev. 2006 Sep; 58(3): 389–462.
 Br J Pharmacol. 2012 Apr;165(8):2485-96. doi:
10.1111/j.1476-5381.2011.01445.x.
 Alexandre S. Crippa, Antonio Waldo Zuardi, Jaime E. C.
Hallak:Therapeutical use of the cannabinoids in psychiatry
 Kenmackie;cannabinoid receptors as therapeutic targets