bmed 443 cannabinoids

8/11/2019 BMED 443 Cannabinoids

1/24

BMED 443: Endocannabinoids and

Medical Marijuana

Instructor: Darrell A. Jackson, Ph.D.


2/24


3/24

THC and Effects

When smoked THC is readily absorbed into blood Euphoria: 2 mg smoked; 5 mg oral

Changes in perceptual time and space: 7 mg smoked;17 mg oral

Changes in body image: 15 mg smoked; 25 mg oral

Pharmacokinetics

THC Half life 19 hours

11-hydroxy-THC half life 50 hours Complete elimination 2-3 weeks


4/24

Behavioral Effects

Low - moderate doses

Loss of inhibition, relaxation, drowsiness

feeling of well being, exhilaration, euphoria

sensory - perceptual changes

recent memory impairment (confusion, memory

lapses and difficulties in concentration)

balance/stability impaired


5/24

Behavioral Effects

High doses Pseudo-hallucinations

Synesthesia

impaired judgment, reaction time

pronounced motor impairment

increasingly disorganized thoughts, confusion,

paranoia, agitation

Not lethal even at very high doses


6/24

Certain parts of the brain govern specific functions. Note the distribution of functions.

Movement is found in the Frontal Lobe.

FrontalLobebody


7/24

When a person smokes marijuana, the active ingredient, cannabinoids or THC, travels quickly

to the brain. Note the areas where THC (magenta) concentrates. The VTA, nucleus accumbens,

caudate nucleus, hippocampus, and cerebellum are highlighted. THC binds to THC receptors

that are concentrated in areas within the reward system as well as these other areas. The action

of THC in the hippocampus explains its ability to interfere with memory and actions in the

cerebellum are responsible for its ability to cause loss of balance and coordination.


8/24

Side Effects

Increased pulse rate

Caffeine, nicotine

Red eye

Decreased salivation No pupil change

cardiovascular (tachycardia)

respiratory (bronchodilation) musculoskeletal (muscle relaxation)

gastrointestinal (decreased motility)


9/24

ENDOCANNABINOID SYSTEM

The firstendocannabinoiddiscovered was namedanandamide (AEA)

A second arachidonic-acid derivative 2-arachidonoylglycerol(2-AG) that binds to

cannabinoid receptorswas subsequentlydescribed


10/24

ENDOCANNABINOID SYSTEM FUNCTION

Postsynaptic neurons synthesize membrane-boundendocannabinoid precursors and cleave them to release activeendocannabinoids following an increase of cytosolic freeCa2+concentrations

Endocannabinoids act as retrograde messengers by binding to

presynaptic CB1cannabinoid receptors, which are coupled tothe inhibition of voltage-sensitive Ca2+channels and theactivation of K+channels.

This blunts membrane depolarization and exocytosis, thereby

inhibiting the release of NTs such as glutamate, dopamineand GABA and affecting, in turn, processes such as learning,movement and memory.


11/24

ENDOCANNABINOID SYSTEM

FUNCTION: Continued

Endocannabinoid neuromodulatory signaling isterminated by an unidentified membrane-transportsystem (T) and a family of intracellular degradativeenzymes, the best characterized of which is fatty acid

amide hydrolase (FAAH), which degrades AEA to AAand Et.

The endogenous cannabinoid system might also exertmodulatory functions outside the brain, both in the

peripheral nervous system and in extra-neural sites,controlling processes such as peripheral pain, vasculartone, intraocular pressure and immune function.


12/24

Endocannabinoid System


13/24

Cannabinoids Receptors


14/24

Effect of THC on hippocampal function


15/24

Medical Uses of Cannabis

1839 On the preparations of the Indian

Hemp, or Gunjah was published by a

British physician (OShaughnessy) working

in India

cannabis preparations were safe (nontoxic)

effective anticonvulsant

muscle relaxant

relieve the pain rheumatisms


16/24

Medical Uses of Cannabis in the USA

1860 Ohio Medical Societyreported on the successfultreatment of stomach pain,chronic cough, and

gonorrhea using C.I ndica

1890s medical textincluded the statementCannabis is very valuablefor the relief of pain,

particularly thatdepending on nervedisturbances.


17/24

Early 20th century

Psychologists usedpsychoactive agents to study

the workings of the mind

French physician, Moreau,

tried to treat a variety of

mental disorders with

hashish

Used to treat cholera,

tetanus, and rabies

Queen Victoria smokedmarijuana for painful

menstrual cramps


18/24


19/24

Medical Uses of Cannabis

(1972) report found marijuana smoking tobe effective in reducing the intraocularpressure in a glaucoma patient

(1975) study showed THC was effective inreducing the severe nausea caused by cancerchemotherapeutic agents

Cachexia treatment Increase appetite


20/24

THC FORMULATIONS

FDA has approved twodrugs, Marinol and

Cesamet, for therapeutic

uses in the U.S., which

contain active ingredientsthat are present in

botanical marijuana.

On December 22, 1992,

FDA approved Marinol

Capsules for the treatment

of anorexia associated with

weight loss in patients with

AIDS.


21/24

THC FORMULATIONS

Bayers new cannabisproduct in Europemarijuana-extractspray called SativexIt provides immediate

symptomatic relief,similar to smokingcannabis, without the

health hazards associatedwith smoking.


22/24

RimonabantRimonabant

CB1

Adipocyte

Brain

CB1

Adiponectin

FA oxidationFA oxidationBody weight

Central

effects

Metabolic

peripheral effects

Rimonabant (CB1 Blocker): A Multi-Impact Drug

Hyperinsulinemia

Insulin sensitivity restored

TG

HDL-C

Control of nicotine

dependence

Decrease in food intake

(palatable and non-

palatable food)

Van Gaal et al; Lancet (2005) 365: 1389-97

The Endocannabinoid System


23/24

States where voter initiatives have allow for

medical use of marijuana

http://online.wsj.com/article/SB10001424052748703626604575011223512854284.html


24/24

bmed 443 cannabinoids

Documents