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, pharmacodynamics, and epidemiology.

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Neuropharmacology: Marijuana

  1. 1. MarijuanaBrian J. Piper, Ph.D.
  2. 2. Goals• History• Epidemiology• Pharmacokinetics• Pharmacodynamics• Medical uses
  3. 3. History• 8,000 BC: archeological records of hemp• 1753 AD: Carl Linnaeus labels Cannabis sativa 1707-1730• 1930s: anti-marijuana propaganda scare tactics
  4. 4. History 1930-• 1964: structure of Δ9-tetrahydrocannabinol discovered followed by Raphael Mechoulam
  5. 5. 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).
  6. 6. 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.
  7. 7. CB1 Density
  8. 8. Density of Cannabinoid Receptor 1 (Increased Darkness = more receptors labeled with [3H]CP-55,940) Hekenham et al. (1991) J Neurosci, 11, 563-583.
  9. 9. 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.
  10. 10. CB1 Species Comparison = =Relative DensityJulien et al. (2011). Primer of Drug Action. p. 485.
  11. 11. 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)
  12. 12. History 1930-•1990s: endogenous cannabinoids identified by RaphaelMechoulam – Anandamide: Sanskrit for “bringer of inner bliss and tranquility”
  13. 13. Backwards
  14. 14. History• 1970: Controlled Substances Act lists MJ as I (marinol as III)• 1996- present: Medical marijuana legalized in 15 states
  15. 15. Medical marijuana (8), decriminalized possession laws (7)Both medical marijuana & decriminalized possession (5)
  16. 16. 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
  17. 17. World Epidemiology UN World Drug Report 2011
  18. 18. MJ Daily by Grade
  19. 19. Epidemiology (MtF)
  20. 20. Availability
  21. 21. MJ by GenderMonitoring the Future (2005) Paper 63http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf
  22. 22. MJ by College PlansMonitoring the Future (2005) Paper 63 http://www.monitoringthefuture.org/pubs/occpapers/occ63.pdf
  23. 23. ER Visits Drug Abuse Warning Network, 2011
  24. 24. 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.
  25. 25. 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%
  26. 26. 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.
  27. 27. 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
  28. 28. Trail Making TestPart A: Draw line connecting #’s Part B: Draw line connecting # -> letter -> #1-2-3-4 1-A-2-B-3-C
  29. 29. 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
  30. 30. -> -> ->Messinis et al. (2006) Neurology, 66, 737-739 Total # Significant Differences 1 12 8
  31. 31. 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.
  32. 32. Spice• Synthetic cannabis is sold online as herbal incense• These are often smoked but do not test result in positive drug screens for THC
  33. 33. Summary• History• PK: ROA• PD: CB1 (anandamide & 2-AG)
  34. 34. Pollan, Michael (2009). The botany of desire. 0:00 to 4:50, 55:50-1:23:30http://www.youtube.com/watch?v=AHUKC8ovPzE

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