Cannabis. Cannabis History of use Material from the Cannabis plants –Cannabis sativa and Cannabis indica Known to have been cultivated for approx. 12,000

Cannabis

Cannabis History of use

• Material from the Cannabis plants

– Cannabis sativa and Cannabis indica

• Known to have been cultivated for approx. 12,000 years (beginning in China)

• Plant stems - rope and linen

• Flowers and seeds & especially a resin on and within them contain the psychoactive chemicals termed Cannabinoids

Cannabis Origins & History of use

• Psychoactive properties were first recorded about 2800 BC in China and 2000 BC in India

• Early uses included rheumatic pains, constipation, malaria, ‘absentmindedness’, menstral cramps, and for its anxiolytic and euphoric properties


• Claims for medicinal and psychiatric uses expanded in the 1800’s and 1900’s as for all drugs

• Hash (the name for the resin) comes from the arabic word hashsha shim (meaning hash eaters- it also spawned the word assasin)


• Marijuana (the name for the dried and crushed flowers) comes from the spanish maraguanaquo (meaning an inebriant plant)

• Cannabis became an illegal substance in North America in the 1920’s

• Revival in marijuana interest occurred in the 60’s


• Marijuana was first used by the Beatles while filming “Hard Day’s Night” (see the snow scene) and flourished along with other “mind expanding drugs (psychedelics) such as LSD and PCP

Cannabis Current Use & Prevalence

• Most widely used illicit drug in the world

• Primary users are teenagers and young adults with use dropping with age (and finer appreciation of wines, single malts and Guiness!)

• North American use was highest in the 70’s but use has ‘levelled off


From the Toronto Drug Survey


• Use in other countries follows different courses (e.g. use in the Netherlands is increasing in the older population)

• Medicinal use is expanding (separate section)

• Revival of the use of hemp & hemp fibre in producing rope, linen, beer etc (all without psychoactive chemicals).

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are:

• Cannabinol (CBN), Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

• THC (-9-THC ) is the only one with significant psychoactive properties

• CBN - 1/10 th activity of THC; CBD - none

Cannabis Pharmacology & Toxicology

• Primary routes of administration are: oral or smoking

• Smoked marijuana or inhaled hash (much more potent) provides the highest delivery

• From a theoretical 69% availability (machine pyrolysis of 1 joint in one puff) actual availability ranges from 10% (infrequent) to 25% (heavy users)


• Typical joint weighs 0.5 - 1 gram and contains 20 + mg of THC

• Therefore it delivers a maximum of 0.2 - 5 mg of THC


• Cannabinoids are highly lipophilic and lipoprotein bound

• Vd = 10 L/Kg• Blood concentrations are therefore not

directly related to drug effect• Release from lipid stores and enterohepatic

recirculation account for retention of THC and terminal half life > 4 days in frequent users.


Huestis et al., 1992, J. Anal. Toxicol., 16:276-290

• Six Volunteers smoked 1 “joint” with 15.8 mg THC over an 11 minute period

• Plasma THC peaked at 50 - 129 ng/mL at 9 minutes (i.e. before they had finished)

• One hour later THC had fallen to 3-20 ng/mL• Levels of 1-2 ng/mL in plasma can persist from

hours to days depending on the frequency of use.


5

10

15

20

2

5

3

0

3

5

40

4

5

50

5

5

0.5 1 2 3 4 5 6 7 81 day 1.5 days 2 days 2.5 days

A

B

C

Triphasic Pharmacokinetics

TH

C c

once

ntra

tion

in n

g/m

L

Time in hrs


• Urine THC can be detected for days after use

• In one instance a frequent marijuana user had THC positive urine for 42 days!


• Passive Inhalation (“Snowboarding Effect”)

• Requires very high concentrations of smoke in a small enclosed area (sometimes requiring goggles)

• Most of these studies identified positive urine tests only (one study reported blood THC 1-6 ng/mL immediately after exposure)

Cannabis Onset & duration of effects

• Physical and psychological effects commence within minutes of finishing a joint

• Psychological effects can persist from 4 to 8 hours depending upon route of administration (oral, slower onset, longer duration)

• Effects do not depend on blood concentration but partially on dose

Cannabis Specific psychological effects

• Effects are dose -dependant and route dependant.

• Effects can generally be felt within 15 minutes and peak effects occur within 30 to 60 minutes post-smoking and last 2-4 hours

• Spectrum of effects precludes classification as a stimulant, sedative or hallucinogen.


• Effects of lower doses include: euphoria, relaxation, wide range from exhilaration to introspection; distortion of time and some visual hallucinations; memory distortions, especially diminished short-term memory and hunger

• Response to higher doses: anxiety, tension, anger, confusion, hallucinations, paranoia and panic attacks.


• THC can unmask manic depressive or schizophrenic patients as will other mood altering, mild hallucinogenic drugs such as MDMA


• Laboratory tests reveal memory deficits (and other impairment described later)

• No objective test of impairment

• Therefore a relative scale of ‘high’ is used e.g. relative to the ‘most stoned you’ve ever been’ is usually employed

• This scale can be used to account for tolerance in frequent vs non-frequent users.


• Wide spectrum of effects fit (to some degree) observed THC interaction with opioid or benzodiazepine receptors.

• Also interaction with organelles and demonstrated ability to inhibit macromolecular metabolism, effect enzyme systems, hormone secretion and neurotransmitters


• Specific Cannabinoid receptors (Central: CB1 & Peripheral: CB2) have been identified in the brain and PNS.

• Endogenous ligands e.g. Anandamide and 2-arachidonyl glycerol have been identified.

• Recent research shows anadamide may be involved in the abolition of ‘extraneous’ short term memories.

Cannabis Specific physiological effects

• Tachycardia (Increased Heart rate)

• Red eye (vasodilation of the conjuctiva) and peripheral vasodilation.

• Increased Blood pressure

• Diminished fine motor control (hand steadiness)

Cannabis Toxicology

• Very wide ‘therapeutic index’

• No known direct deaths

• Fatal dose is unknown, but implied from animal studies may be 4000 to 40000 times the highest recreational dose.

• Implied association with deaths due to underlying heart conditions especially arrythmias/ heart attacks; not confirmed

Cannabis Clinical Uses

• Synthetic THC Marinol®, dronabinol

• Bioavailability is 10-20% of IV (high first pass effect).

• t 1/2 ~ 60 hrs

• prescribed for severe nausea & vomiting associated with chemotherapy

• Side effects: sedation, mode altered (laughing, elation), confusion...


“Medical Marijuana”

• Low bioavailability of dronabinol have lead to the ‘experimental’ use of smoked MJ in clinical research

• MJ use in glaucoma (reduction in hypertension) has been established

• Appetite enhancement is also established and useful for AIDS and cancer patients


“Medical Marijuana”• Reported to have antispasmodic and pain

reduction properties in the treatment of Multiple Sclerosis (antispasmodic & analgesic; mostly subjective evidence to date).

• Other studies are focusing on analgesis, anti-inflammatory, antitumor and anti-epileptic possibilities



• Very few clinical studies of actual benefits of cannabis in treating medical conditions

• Most of the information is anecdotal and ‘popular’ (i.e. produced by activists outside of the oppressive establishment and therefore true by definition).



• Canada is was the only country which allows Medical use (medical exemption by ‘prescription’; physicians are allowed to prescribe drugs in whatever dose and for whatever reason they deem fit/e.g. pediatrics and & psychiatry)



• However, Health Canada is still investigating claims of the effectiveness of cannabis (one stated use of the MJ crop being grown for Health Canada).



• Thus Medical MJ users live in a ‘Catch 22’ situation… they can possess MJ, Health Canada grows its, but will not provide it yet… they must obtain seeds etc illegally, but once in their possession, it’s legal.

Cannabis Toxicology

Results of consuming a psychoactive agent with hallucinogenic and sedative properties

1) Sexual assault

2) Driving

Cannabis Toxicology:DFSA

• Cannabis is the second-most common drug in sexual assaults, next to alcohol

• This is probably due more to the wide-spread use of the drug, rather than an attempt to ‘incapacitate’ another individual

• Yet, MJ sedating & memory reducing effects will enhance the effects of CNS depressants

Cannabis Toxicology: Impaired by THC

• THC has been implicated with other drugs and alcohol in contributing to vehicular accidents and fatalities for many years from epidemiological data

• One major problem is the concomittant use of alcohol and marijuana.

• Impediment to determining the actual contribution of THC to impairment


• Laboratory studies

• THC impairs: divided attention, short term memory, concentrated attention, emergency situation reaction times, speed regulation.

• Appears to improve some aspects relative to alcohol: drivers appear more cautious, willing to take less risks, give more headway


• Headway abolished with higher doses

• ‘Caution’ (timidity) may prove dangerous in heavy traffic or in emergency situations

• Suggestion that users can compensate (similar to alcohol at 10-20 mg% in adults)

• Visual/temporal distortions, memory deficits and inability to remain focused however, can’t be fully compensated


• Studies also may use unrealistic amounts of cannabis, based on perceived high (e.g. drug highs depend upon social interaction, setting etc)

• One study, Robbe, (1994, Inst Hum Psychopharmacol) used significantly higher doses, but would not test impairment at the higher doses on a city street, due to safety concerns despite claiming that MJ had a significant, but not dramatic impairing effect


• Closed/Open course Driving Studies show impairment of:

• road tracking (standard deviation of lateral position or ability to stay within a lane)

• ‘cautious’ headway at low doses; lost at higher (relevant) doses.

• Vigilance also appears to be reduced

• Few studies to date


• Study by Ramaekers et al

• Measured the effects of THC & alcohol

• Found significant impairing effects at blood alcohol concentrations as low as 35 mg% (equal as little as 1 beer in women and 2 beers in men)

Documents

Cannabis. Cannabis History of use Material from the Cannabis plants –Cannabis sativa and Cannabis indica Known to have been cultivated for approx. 12,000