Psychopharmacology

, Volume 212, Issue 4, pp 675–686 | Cite as

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study

  • Gillinder Bedi
  • Richard W. Foltin
  • Erik W. Gunderson
  • Judith Rabkin
  • Carl L. Hart
  • Sandra D. Comer
  • Suzanne K. Vosburg
  • Margaret Haney
original investigation

Abstract

Rationale

Dronabinol (Δ9tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects.

Objectives

Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication.

Methods

Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1–8 and 9–16; we compared dronabinol’s effects with placebo in each 8-day phase to investigate tolerance.

Results

Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol’s mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects.

Conclusions

In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.

Keywords

HIV Dronabinol THC Appetite stimulation Anorexia 

References

  1. Abrams DI (1998) Medical marijuana: trials and tribulations. J Psychoactive Drugs 30:163–169PubMedGoogle Scholar
  2. Abrams DI (2000) Potential interventions for HIV/AIDS wasting: an overview. JAIDS 25:S74–S80PubMedGoogle Scholar
  3. Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, Benowitz NL, Bredt BM, Kosel B, Aberg JA, Deeks SG, Mitchell TF, Mulligan K, Bacchetti P, McCune JM, Schambelan M (2003) Short-term effects of cannabinoids in patients with HIV-1 infection. Ann Intern Med 139:258–266PubMedGoogle Scholar
  4. American Psychiatric Association (1994) DSM-IV: diagnostic and statistical manual of mental disorders. American Psychiatric AssociationGoogle Scholar
  5. Ashton CH (2001) Pharmacology and effects of cannabis: a brief review. Br J Psychiatry 178:101–106CrossRefPubMedGoogle Scholar
  6. Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10:89–97CrossRefPubMedGoogle Scholar
  7. Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, Morales JO, Murphy R, Powderly W, Plasse TF, Mosdell KW, Shepard KV (1997) Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage 14:7–14CrossRefPubMedGoogle Scholar
  8. Chubineh S, McGowan J (2008) Nausea and vomiting in HIV: a symptom review. Int J STD AIDS 19:723–728CrossRefPubMedGoogle Scholar
  9. Dansak DA (1997) Medical use of recreational drugs by AIDS patients. J Addict Dis 16:25–30CrossRefPubMedGoogle Scholar
  10. Davidson ES, Schenk S (1994) Variability in subjective responses to marijuana: initial experiences of college students. Addict Behav 19:531–538CrossRefPubMedGoogle Scholar
  11. D’Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J (2008) Blunted psychotomimetic and amnestic effects of delta-9-tetracannabinol in frequent users of cannabis. Neuropsychopharmacology 33:2505–2516CrossRefPubMedGoogle Scholar
  12. Evans SM, Foltin RW, Fischman MW (1999) Food “cravings” and the acute effects of alprazolam on food intake in women with premenstrual dysphoric disorder. Appetite 32:331–349CrossRefPubMedGoogle Scholar
  13. Folstein MF, Luria R (1973) Reliability, validity, and clinical application of the visual analogue mood scale. Psychol Med 3:479–486CrossRefPubMedGoogle Scholar
  14. Furler MD, Einarson TR, Millson M, Walmsley S, Bendayan R (2004) Medicinal and recreational marijuana use by patients infected with HIV. AIDS Patient Care STDs 18:215–228CrossRefPubMedGoogle Scholar
  15. Grinspoon L, Bakalar JB (1997) Marihuana: the forbidden medicine. Yale University Press, New HavenGoogle Scholar
  16. Hall W, Degenhardt L (2003) Medical marijuana initiatives. Are they justified? How successful are they likely to be? CNS Drugs 17:689–697CrossRefPubMedGoogle Scholar
  17. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999a) Abstinence symptoms following oral THC administration to humans. Psychopharmacology 141:385–394CrossRefPubMedGoogle Scholar
  18. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999b) Abstinence symptoms following smoked marijuana in humans. Psychopharmacology 141:395–404CrossRefPubMedGoogle Scholar
  19. Haney M, Bisaga A, Foltin RW (2003) Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology 166:77–85PubMedGoogle Scholar
  20. Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, Foltin RW (2004) Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology 29:158–170CrossRefPubMedGoogle Scholar
  21. Haney M, Rabkin J, Gunderson EW, Foltin RW (2005) Dronabinol and marijuana in HIV + marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology 181:170–178CrossRefPubMedGoogle Scholar
  22. Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, Foltin RW (2007) Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood and sleep. JAIDS 45:545–554PubMedGoogle Scholar
  23. Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW (2008) Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology 197:157–168CrossRefPubMedGoogle Scholar
  24. Hart CL, Haney M, Ward AS, Fischman MW, Foltin RW (2002a) Effects of oral THC maintenance on smoked marijuana self-administration. Drug Alcohol Depend 67:301–309CrossRefPubMedGoogle Scholar
  25. Hart CL, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW (2002b) Comparison of smoked marijuana and oral Δ9-tetrahydrocannabinol in humans. Psychopharmacology 164:407–415CrossRefPubMedGoogle Scholar
  26. Hazekamp A, Ruhaak R, Zuurman L, Van Gerven J, Verpoorte R (2006) Evaluation of a vaporizing device (Volcano®) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci 95:1308–1317CrossRefPubMedGoogle Scholar
  27. Hollister LE (2000) An approach to the medical marijuana controversy. Drug Alcohol Depend 58:3–7CrossRefPubMedGoogle Scholar
  28. Hunt CA, Jones RT (1980) Tolerance and disposition of tetrahydrocannabinol in man. J Pharmacol Exp Ther 215:35–44PubMedGoogle Scholar
  29. Institute of Medicine (1999) Marijuana and medicine: assessing the science base. Institute of Medicine, Washington DCGoogle Scholar
  30. Johanson C, Uhlenhuth E (1980) Drug preference and mood in humans: diazepam. Psychopharmacology 71:269–273CrossRefPubMedGoogle Scholar
  31. Johnson M, Charlebois E, Morin SF, Catz SL, Goldstein RB, Remien RH, Rotheram-Borus MJ, Mickalian JD, Kittel L, Samimy-Muzaffar F, Lightfoot MA, Gore-Felton C, Chesney A, Team NHLP (2005) Perceived adverse effects of antiretroviral therapy. J Pain Symptom Manage 29:193–205CrossRefPubMedGoogle Scholar
  32. Kirk JM, de Wit H (1999) Responses to oral tetrahydrocannabinol in frequent and infrequent marijuana users. Pharmacol Biochem Behav 63:137–142CrossRefPubMedGoogle Scholar
  33. Martin BR (2002) Medical marijuana: moving beyond the smoke. Lancet 360:4–5CrossRefPubMedGoogle Scholar
  34. Mehra R, Moore BA, KC TJ, Fiellin DA (2006) The association between marijuana smoking and lung cancer: a systematic review. Arch Int Med 166:1359–1367CrossRefGoogle Scholar
  35. Parrott AC, Garnham NJ, Wesnes K, Pincock C (1996) Cigarette smoking and abstinence: comparative effects upon cognitive task performance and mood state over 24 hours. Hum Psychopharmacol Clin Exp 11:391–400CrossRefGoogle Scholar
  36. Prentiss D, Power R, Balmas G, Tzuang G, Israelski D (2004) Patterns of marijuana use among patients with HIV/AIDS followed in a public health care setting. JAIDS 35:38–45PubMedGoogle Scholar
  37. Ramaekers JG, Kauert G, Theunissen E, Toennes S, Moeller M (2009) Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. J Psychopharmacol 23:266–277CrossRefPubMedGoogle Scholar
  38. Sachse-Seeboth C, Pfeil J, Sehrt D, Meineke I, Tzvetkov M, Bruns E, Poser W, Vormfelde SV, Brockmoller J (2009) Interindividual variation in the pharmacokinetics of Delta-9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. Clin Pharmacol Ther 85:273–276CrossRefPubMedGoogle Scholar
  39. Sheskin DJ (2000) Handbook of parametric and nonparametric statistical procedures, 2nd edn. CRC Press LLC, Boca RatonGoogle Scholar
  40. Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, Ries K, Evans TG (1993) Effect of dronabinol on nutritional status in HIV infection. Ann Pharmacother 27:827–831PubMedGoogle Scholar
  41. Taylor D, Poulton R, Moffitt TE, Ramankutty P, Sears MR (2000) The respiratory effects of cannabis dependence in young adults. Addiction 95:1669–1677CrossRefPubMedGoogle Scholar
  42. Taylor DR, Fergusson DM, Milne BJ, Horwood LJ, Moffitt TE, Sears MR, Poulton R (2002) A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults. Addiction 97:1055–1061CrossRefPubMedGoogle Scholar
  43. Wanke CA, Silva M, Knox TA, Forrester J, Speigelman D, Gorbach SL (2000) Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 31:803–805CrossRefPubMedGoogle Scholar
  44. Ware M, Rueda S, Singer J, Kilby D (2003) Cannabis use by persons living with HIV/AIDS: patterns and prevalence of use. J Cannabis Ther 3:3–15CrossRefGoogle Scholar
  45. Woolridge E, Barton S, Samuel J, Osorio J, Dougherty A, Holdcroft A (2005) Cannabis use in HIV for pain and other medical symptoms. J Pain Symptom Manage 29:358–367CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gillinder Bedi
    • 1
    • 2
  • Richard W. Foltin
    • 1
    • 2
  • Erik W. Gunderson
    • 1
    • 2
  • Judith Rabkin
    • 1
    • 2
  • Carl L. Hart
    • 1
    • 2
  • Sandra D. Comer
    • 1
    • 2
  • Suzanne K. Vosburg
    • 1
    • 2
  • Margaret Haney
    • 1
    • 2
  1. 1.Department of PsychiatryCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA
  2. 2.Division on Substance AbuseNew York State Psychiatric InstituteNew YorkUSA

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