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Neuropharmacology: Marijuana
 

Neuropharmacology: Marijuana

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Lecture 16 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Covers pharmacokinetics, ...

Lecture 16 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Covers pharmacokinetics, pharmacodynamics, and epidemiology.

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    Neuropharmacology: Marijuana Neuropharmacology: Marijuana Presentation Transcript

    • MarijuanaBrian J. Piper, Ph.D.
    • Goals• History• Epidemiology• Pharmacokinetics• Pharmacodynamics• Medical uses
    • History• 8,000 BC: archeological records of hemp• 1753 AD: Carl Linnaeus labels Cannabis sativa 1707-1730• 1930s: anti-marijuana propaganda scare tactics
    • History 1930-• 1964: structure of Δ9-tetrahydrocannabinol discovered followed by Raphael Mechoulam
    • Pharmacokinetics Injection Smoking Oral 100 100 100 THC Blood levels 1 1 1 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 5 6 Time (hr) Time (hr)Route of administration influences THC pharmacokinetics, left = 5 mg i.v. injection,center = smoking 13.0 mg, or right =consuming cookie with 20 mg (Agurell et al. 1986).
    • 10 Intravenous (5 mg) Smoking (19 mg) Oral (20 mg)Rated“high” 0 120 240 360 0 Time (min) Agurell et al. (1986) Pharmacol Review 38, 21-43.
    • CB1 Density
    • Density of Cannabinoid Receptor 1 (Increased Darkness = more receptors labeled with [3H]CP-55,940) Hekenham et al. (1991) J Neurosci, 11, 563-583.
    • Spatial MemoryInfusion of THC into the dorsal (A) or ventral (B) hippocampusincreased errors in the radial arm maze.Egashira et al. Brain Research 952(2), 239-245.
    • CB1 Species Comparison = =Relative DensityJulien et al. (2011). Primer of Drug Action. p. 485.
    • Effects of THC on dopamine 1.0 mg/kg THC 0.5 mg/kg THC 150 Vehicle% change inaccumbens DA 100 Injection 0 40 80 120 Time (min)
    • History 1930-•1990s: endogenous cannabinoids identified by RaphaelMechoulam – Anandamide: Sanskrit for “bringer of inner bliss and tranquility”
    • Backwards
    • History• 1970: Controlled Substances Act lists MJ as I (marinol as III)• 1996- present: Medical marijuana legalized in 15 states
    • Medical marijuana (8), decriminalized possession laws (7)Both medical marijuana & decriminalized possession (5)
    • Medical Marijuana• 1998 IOM report concluded that there is scientific evidence for the medical use of marijuana – Analgesic – Peripheral and central – Anti-emetic – Anti-spastic – Appetite Stimulant – Glaucoma
    • World Epidemiology UN World Drug Report 2011
    • MJ Daily by Grade
    • Epidemiology (MtF)
    • Availability
    • MJ by GenderMonitoring the Future (2005) Paper 63http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf
    • MJ by College PlansMonitoring the Future (2005) Paper 63 http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf
    • ER Visits Drug Abuse Warning Network, 2011
    • Drug Education• Comparison of 3 types: – D.A.R.E. – Noninteractive: expert – Interactive: peer to peer d = (Meanprogram – Meanno program) / SD 0.00 = no effect 0.20 small effect 0.50 moderate effectEnnett et al. (1994). American Journal of Public Health, 84(9), 1394-1401.
    • THC CH 3 OH H 3C CH 2 CH 2 H 3C O CH 2 CH 2 CH 3 ∆ 9-TetrahydrocannabinolMarijuana: 3%Hashish: 8%Hash oil: 50%
    • Repeated Administration Vehicle 14 Days of THC[3H]CP-55,940 binding following 14 days of 10 mg/kg THC or vehicle to rats.Oviedo et al. (1993) Brain Res, 616, 293-302.
    • Subtle Neuropsychological Impairment? • Subjects: – 20 Heavy/Long-term MJ users (4+ joints/week for 10 years) – 20 Heavy/Short-term MJ users (4+ joints/week for 5-9 years) – 24 Control subjects • Tests (24 hours MJ free): – Rey Auditory Verbal Learning Test (RAVLT): verbal learning/memory – Trail Making Test (TMT): Motor speed/attention – Beck Depression Inventory (BDI) Messinis et al. (2006) Neurology, 66, 737-739.http://portal.wpspublish.com/portal/page?_pageid=53,70251&_dad=portal&_schema=PORTAL
    • Trail Making TestPart A: Draw line connecting #’s Part B: Draw line connecting # -> letter -> #1-2-3-4 1-A-2-B-3-C
    • Trail Making Test Mean (SEM) Trail Making Test: A Mean (SEM) Trail Making Test: B 60 125 * * * * 50 100 40 Seconds 75 Seconds 30 50 20 10 25 0 0 Control Short MJ Long MJ Control Short MJ Long MJMessinis et al. (2006) Neurology, 66, 737-739
    • -> -> ->Messinis et al. (2006) Neurology, 66, 737-739 Total # Significant Differences 1 12 8
    • Withdrawal from MJ?• Long-term MJ (N=7) users (6 days/week, 4 joints/day) lived in a laboratory• The 5-HT/NE reuptake inhibitor Nefazodone was adminstered. DaysHaney (2002). J Clinical Pharmacology, 42, 34S-40S.
    • Spice• Synthetic cannabis is sold online as herbal incense• These are often smoked but do not test result in positive drug screens for THC
    • Summary• History• PK: ROA• PD: CB1 (anandamide & 2-AG)
    • Pollan, Michael (2009). The botany of desire. 0:00 to 4:50, 55:50-1:23:30http://www.youtube.com/watch?v=AHUKC8ovPzE