Psychiatric Pharmacy Essentials: Medication Interactions with Non-medical Psychoactive Substances

Due to the potential for concomitant psychiatric illness and substance use, understanding the potential interactions between prescription medications and non-medically used psychoactive substances is important.

  • What are some potential drug-drug interactions between illicit drugs and prescription medications?1-3
  • How does cigarette smoking (polycyclic aromatic hydrocarbons) affect medications?4-5
  • What are possible drug interactions in patients that consume alcohol?6-7
  • How do opioids and benzodiazepines interact? What is the clinical significance of the combination?8-10
  • How do illicit drugs interact with anti-retroviral therapies?11-12
  • How do natural or synthetic cannabis products interact with prescription medications?13-20

Reviewer 1: Bridgette Gleisner, PharmD, BCPP
Reviewer 2: Roisin Sabol, PharmD, BCPP
2026-2027 AAPP Resident and New Practitioner Committee

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  2. Abbott KL, Flannery PC, Gill KS, Boothe DM, Dhanasekaran M, Mani S, et al. Adverse pharmacokinetic interactions between illicit substances and clinical drugs. Drug Metabolism Rev. 2020 Jan 2;52(1):44-65. Informa UK Limited. DOI: 10.1080/03602532.2019.1697283.
  3. Lindsey WT, Stewart D, Childress D. Drug Interactions between Common Illicit Drugs and Prescription Therapies. Am J Drug Alcohol Abus. 2012 Jul 1;38(4):334-343. Informa UK Limited. DOI: 10.3109/00952990.2011.643997.
  4. Kroon LA. Drug interactions with smoking. American Journal of Health-System Pharmacy. 2007 Sep 15;64(18):1917-1921. Oxford University Press (OUP). DOI: 10.2146/ajhp060414.
  5. Kohut SJ. Interactions between nicotine and drugs of abuse: a review of preclinical findings. Am J Drug Alcohol Abus. 2017 Mar 4;43(2):155-170. Informa UK Limited. DOI: 10.1080/00952990.2016.1209513.
  6. Holton AE, Gallagher P, Fahey T, Cousins G. Concurrent use of alcohol interactive medications and alcohol in older adults: a systematic review of prevalence and associated adverse outcomes. BMC Geriatr. 2017 Dec;17(1). Springer Science and Business Media LLC. DOI: 10.1186/s12877-017-0532-2.
  7. Qato DM, Manzoor BS, Lee TA. Drug–Alcohol Interactions in Older U.S. Adults. J Am Geriatrics Soc. 2015 Nov;63(11):2324-2331. Wiley. DOI: 10.1111/jgs.13787.
  8. Xu KY, Hartz SM, Borodovsky JT, Bierut LJ, Grucza RA. Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015. JAMA Netw open. 2020 Dec 9;3(12):e2028557. American Medical Association (AMA). DOI: 10.1001/jamanetworkopen.2020.28557.
  9. McCance‐Katz EF, Sullivan LE, Nallani S. Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A Review. Am J Addict. 2010 Jan;19(1):4-16. Wiley. DOI: 10.1111/j.1521-0391.2009.00005.x.
  10. FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults. CMR. 2018 May 16. Case Journals. DOI: 10.31525/fda2-ucm607884.htm.
  11. Desai N, Burns L, Gong Y, Zhi K, Kumar A, Summers N, et al. An update on drug–drug interactions between antiretroviral therapies and drugs of abuse in HIV systems. Expert Opin Drug Metabolism & Toxicol. 2020 Nov;16(11):1005-1018. Informa UK Limited. DOI: 10.1080/17425255.2020.1814737.
  12. Cernasev A, Veve MP, Cory TJ, Summers NA, Miller M, Kodidela S, et al. Opioid Use Disorders in People Living with HIV/AIDS: A Review of Implications for Patient Outcomes, Drug Interactions, and Neurocognitive Disorders. Pharmacy. 2020 Sep 11;8(3):168. MDPI AG. DOI: 10.3390/pharmacy8030168.
  13. Arellano AL, Papaseit E, Romaguera A, Torrens M, Farré M. Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids with Drugs of Abuse and Medicines. CNSNDDT. 2017 Aug 9;16(5). Bentham Science Publishers Ltd.. DOI: 10.2174/1871527316666170413104516.
  14. Kong TY, Kim JH, Kim DK, Lee HS. Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes. Arch Pharm Res. 2018 Jul;41(7):691-710. Springer Science and Business Media LLC. DOI: 10.1007/s12272-018-1055-x.
  15. Brown J, Winterstein A. Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. JCM. 2019 Jul 8;8(7):989. MDPI AG. DOI: 10.3390/jcm8070989.
  16. Qian Y, Gurley BJ, Markowitz JS. The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. J Clin Psychopharmacol. 2019 Sep;39(5):462-471. Ovid Technologies (Wolters Kluwer Health). DOI: 10.1097/jcp.0000000000001089.
  17. Brown JD. Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions. JCM. 2020 Mar 27;9(4):919. MDPI AG. DOI: 10.3390/jcm9040919.
  18. Doohan PT, Oldfield LD, Arnold JC, Anderson LL. Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization. AAPS J. 2021 Jul;23(4). Springer Science and Business Media LLC. DOI: 10.1208/s12248-021-00616-7.
  19. Anderson GD, Chan LN. Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Clin Pharmacokinet. 2016 Nov;55(11):1353-1368. Springer Science and Business Media LLC. DOI: 10.1007/s40262-016-0400-9.
  20. Nachnani R, Knehans A, Neighbors JD, Kocis PT, Lee T, Tegeler K, et al. Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis. Front Pharmacol. 2024 May 22;15. Frontiers Media SA. DOI: 10.3389/fphar.2024.1282831.