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Marijuana

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Passage of Marijuana Tax Act of 1937 ... Accounted for 1% of all confiscated marijuana samples in the past ten years. Marijuana - dried flowering tops and leaves ... – PowerPoint PPT presentation

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Title: Marijuana


1
Marijuana
  • Carl L. Hart, Ph.D.
  • Division on Substance Abuse, New York State
    Psychiatric Institute, Department of Psychiatry,
    College of Physicians and Surgeons, and
    Department of Psychology, Columbia University

2
ASAMs 2008 Review Course in Addiction Medicine
  • ACCME required disclosure of
  • relevant commercial relationships
  • Dr. Hart discloses that he has received honoraria
    from Shire, Inc.,
  • for consulting services .

3
Brief Recent History
  • Late 1920s marijuana associated with crime and
    ethnic minorities
  • Public concern aroused
  • Passage of Marijuana Tax Act of 1937
  • When 1937 tax act was passed, MJ was not
    regulated by the same system as the opioids and
    cocaine--intent was to eliminate its use
  • May 1969 ruled unconstitutional
  • Controlled Substance Act of 1970

4
Marijuana Constituents
  • Contains a complex mixture of over 400 chemicals
  • 66 are cannabinoids
  • ?9-THC is the primary psychoactive constituent

5
Common Forms of Cannabis
  • Hashish - dried resin and compressed flowers
  • ?9-THC content ranged from 3 to 7 with rare
    increases as high as about 20
  • Accounted for samples in the past ten years
  • Marijuana - dried flowering tops and leaves
  • Wide range of ?9-THC content with rare increases
    as high as about 26
  • most common form

6
Marijuana Current Prevalence
  • Most widely used illicit drug in the world
  • 150 million annual users (amphetamines 34
    million)

7
Marijuana Prevalence
  • In the U.S., 50 of young adults (18-25 yrs old)
    report annual use
  • 15 million current users (past month use)
  • 2 million new users (stable since mid-1990s)
  • Concern about use by youth

8
MTF Marijuana Use
9
MTF Marijuana Use
10
MTF Marijuana Use
11
?9-THC in U.S. Confiscated Marijuana
12
Significance of modest ?9-THC increase?
  • Public officials express concern about
    marijuana-related negative effects
  • e.g., dependence, toxicity
  • Similar psychoactive effects, but more pronounced

13
Pharmacology
  • Receptors
  • CB1 (primarily in brain)
  • CB2 (immune system)

14
Brain regions rich with cannabinoid receptors
Function
Region
  • Nigrostriatal region
  • Cerebellum
  • Hippocampus
  • Nucleus accumbens
  • Cerebral cortex
  • Moderate Levels
  • Hypothalamus
  • Amygdala
  • Brain stem
  • Spinal cord
  • Movement
  • Fine motor movements
  • Learning and memory
  • Drug reinforcement
  • Higher cognitive functions
  • Temperature regulation
  • Emotionality
  • Sleep and arousal, nausea
  • Pain

15
Abuse Potential
  • Rats and squirrel monkeys will consistently
    self-administer cannabinoids
  • Human marijuana smokers robustly self-administer
    marijuana
  • Self-administration related to ?9-THC content of
    the cigarettes
  • In U.S., 7 million classified as dependent or
    abuser of illicit drugs
  • Marijuana accounted for 4 million
  • More people sought treatment for marijuana than
    any other illicit drug

16
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (euphoria)?

17
Smoked Marijuana Subjective Effects
Hart et al. 2001, Neuropsychopharmacology
18
Oral ?9-THC Subjective Effects
Hart et al. accepted, pending revisions
19
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Some negative effects in infrequent smokers
  • Anxiety
  • Mild paranoia and hallucinations

20
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate?

21
Smoked Marijuana Heart Rate
Hart et al. 2001, Neuropsychopharmacology
22
Oral ?9-THC Heart Rate
Hart et al. 2005, Psychopharmacology
23
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake?
  • Medical marijuana issue

24
Possible Medical Uses for Marijuana
  • Chemotherapy-induced nausea
  • Marinol (dronabinol) ?9-THC in sesame oil in a
    gelatin capsule
  • FDA-approved in 1985
  • Appetite stimulant for AIDS wasting
  • FDA-approved in 1992
  • Various types of pain
  • Glaucoma
  • Anticonvulsant
  • Multiple Sclerosis-related spasticity

25
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake?

26
Total Caloric intake
Hart et al. 2002, Psychopharmacology
27
Individual Data
Hart et al. 2002, Psychopharmacology
28
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake (increased)
  • Cognitive effects?

29
Smoked Marijuana Acute Cognitive Effects
  • Cognitive performance is disrupted temporarily in
    several domains
  • slowed cognitive processing
  • impaired short-term memory
  • impaired inhibitory control
  • loss of sustained concentration or vigilance
  • impaired visuospatial processing
  • Cognitive effects are dose-related
  • Cognitive effects less dramatic in frequent
    smokers
  • Perhaps due to tolerance

30
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake (increased)
  • Cognitive effects (variable)
  • Driving ability?

31
Driving Ability
  • Findings have been inconsistent
  • Epidemiological studies
  • Little evidence that drivers who use marijuana
    alone are more likely to be involved in an
    accident than non-drug using drivers
  • Laboratory studies
  • Computer-controlled driving simulator data
    indicate that marijuana produces significant
    impairments

Ramaekers et al. 2004, Drug and Alcohol Dependence
32
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake (increased)
  • Cognitive effects (variable)
  • Driving ability (depends on model used)
  • Does marijuana cause psychotic illness?

33
Psychotic illness
  • Association between between marijuana and illness
    not well understood
  • Marijuana use can precipitate psychotic episodes
  • No evidence that marijuana can cause the
    underlying psychotic disorder

34
Basic Pharmacology Review of Acute Effects
  • Abuse Potential (high)
  • Positive subjective effects (increased)
  • Heart rate (increased)
  • Food intake (increased)
  • Cognitive effects (variable)
  • Driving ability (depends on model used)
  • Does marijuana cause psychotic illness (unclear)
  • Verbal Behavior (decreased)
  • Dry mouth
  • Reddened eyes

35
Consequences of Chronic Marijuana Smoking
  • Physical dependence?

36
Cannabinoid Withdrawal in Laboratory Animals
  • SR 141716A, a CB1 cannabinoid antagonist produces
    a reliable withdrawal syndrome in laboratory
    animals undergoing chronic cannabinoid treatment
  • Symptoms
  • wet-dog shakes, paw tremors, piloerection, and
    increased grooming
  • reduced DAergic activity in the VTA-NAc pathway,
    and upregulated expression and release of CRH in
    the central nucleus of the amygdala

37
Medication effects on precipitated cannabinoid
withdrawal symptoms
Hart 2005, Drug and Alcohol Dependence
38
DSM-IV-TR Substance Dependence
  • Three or more occurring in same 12-month period
  • 1) tolerance
  • 2) withdrawal
  • 3) uses more or over longer period than intended
  • 4) persistent desire or unsuccessful efforts to
    cut down or control use
  • 5) a great deal of time spent in activities
    necessary to obtain substance
  • 6) important social, occupational, recreational
    activities reduced or given up because of the
    substance
  • 7) continued use despite recurrent
    substance-related physical or psychological
    problem(s)

39
Consequences of Chronic Marijuana Smoking
  • Physical dependence
  • In laboratory animals (yes)
  • In human?

40
Marijuana Withdrawal in Humans
  • Observed following abrupt cessation of several
    days of cannabis administration
  • Generally, only observed in heavy users
  • Symptoms include
  • increased anxiety, restlessness, depression, and
    irritability
  • disrupted sleep, decreased food intake
  • Symptoms
  • begin 1 day after cannabinoid cessation and
    persist from 4 to 14 days, depending on an
    individuals level of dependence.

41
Medication effects on marijuana withdrawal
symptoms
Hart 2005, Drug and Alcohol Dependence
42
Consequences of Chronic Marijuana Smoking
  • Physical dependence (yes)
  • Cognitive impairment?

43
Smoked Marijuana Long-term Cognitive Effects
  • Data have been inconclusive
  • Subtle deficits following brief abstinence
  • Short-term memory
  • In general, following a sufficient abstinent
    period ( 1 month), regular marijuana use appears
    to produce minimal effects on cognition as
    measured by standard neuropsychological tests

44
Consequences of Chronic Marijuana Smoking
  • Physical dependence (yes)
  • Cognitive impairment (inconclusive)
  • High risk groups?

45
Consequences of Smoking Marijuana High Risk
Groups
  • Individuals with pre-existing diseases
  • Cardiovascular
  • Respiratory diseases, chronic bronchitis
  • Schizophrenia, depression
  • Dependence on other substances

46
Take-home Message
  • Much has been learned about marijuana-related
    effects, but much remains unknown
  • Important considerations
  • Acute vs long-term effects
  • Account for marijuana use history
  • Account for co-occurring illnesses
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