Alzheimer's Disease and Medical Cannabis

Is medicinal cannabis addictive?

With medical cannabis being legal in Australia, many ask whether it's addictive.

Medicinal cannabis is being increasingly legally prescribed in Australia and around the world for a range of medical conditions. As a result, it is understandable that doctors and patients have expressed concern regarding the potential risk of addiction or dependence. One of the problems faced in assessing this risk is that cannabis use disorder (CUD) has been widely studied in recreational users but not in patients using cannabis for medicinal purposes. Because there are large differences between recreational use and medical use, neither the methods and measures used to assess CUD, nor the findings of these studies may be relevant or appropriate for patients¹.

How is dependence different from addiction?

Addiction to a drug is an acquired, chronic, relapsing disorder that is characterised by a powerful motivation to continually take the drug despite persistent negative consequences. On the other hand, dependence can occur without drug-seeking behaviours or persistent negative consequences. Dependence is therefore a more appropriate term when referring to medicinal cannabis use¹.

Dependence can be physical and psychological. According to Prof Valerie Curran, a clinical psychopharmacologist at University College London, physical dependence causes withdrawal symptoms after stopping medication use. This occurs due to the body’s adaptation to the drug and the body’s response to compensate for the drug’s actions. Psychological dependence involves powerfully motivating cognitive processes that maintain medication consumption to avoid the expected negative consequences of stopping use², such as a return of symptoms. 

Prof Curran emphasises that it is important not to confuse the desire to continue taking a medication – and this applies to any medication, including paracetamol – that treats unpleasant or painful chronic symptoms which return when the drug is stopped, with the craving of addiction or with dependence¹.

What are the differences between recreational and medicinal use?

The major differences lie in routes of administration, dosage, forms of cannabis, and cannabinoid ratios. Each of these can significantly affect the potential for dependence, as can context¹.  For example, recreational users desire to experience the rapid euphoric effects of smoked cannabis, while medical cannabis users stop medical use due to these effects³, and tend to prefer oral products which are metabolised more slowly thus reducing the intensity of side effects. 

Tetrahydrocannabinol (THC), the most abundant intoxicating cannabinoid in cannabis, is classed as a Schedule 1 drug under the United Nations Convention on Psychotropic Substances as it has the capacity to create dependence (United Nations, 1971).  In Australia, THC is a Schedule 8 controlled drug available only under prescription. THC produces the psychoactive effects recreational users look for, and who report liking it and wanting more⁴. Studies show that the risk of recreational cannabis dependence is more common with high strength THC cannabis strains with a low CBD content (bred illegally for this purpose), large amounts consumed, high frequency use (heavy, daily) and with starting use early in adolescence⁵. These scenarios are quite different to those in a medical setting, where adult patients are prescribed legal formulations prepared from low strength THC cannabis strains, usually in combination with CBD, in low doses and titrated slowly in order to treat a chronic condition, and under medical supervision. 

Medicinal THC and risk of dependence

In spite of the differences between recreational and medical use, the United Nations’ Report of the International Narcotics Control Board (2018) has concluded that dependence is a probable outcome of daily medicinal cannabis use. People using formulations containing THC on a daily basis (such as for chronic pain) may be at greater risk of dependence than those using it weekly.

Currently, there is very limited research looking at whether there is an association between medicinal THC and dependence, hence appropriate studies addressing this are urgently needed. In the meantime, existing policies will continue to regulate both recreational and medicinal use. 

This highlights the importance for people considering medicinal cannabis as a treatment to do so under the advice and supervision of a registered medical practitioner.

Medicinal CBD and risk of dependence

Cannabidiol (CBD) is the most abundant non-intoxicating cannabinoid in cannabis, and according to the World Health Organization (WHO), it has no abuse potential⁶ . CBD has a complex range of pharmacological actions and although it can control brain processes just like THC, there is no evidence to suggest that it causes dependence. In fact, some studies indicate that CBD may have anti-addictive properties⁷. One of these studies, a randomised controlled trial of three doses of CBD and matched placebo, found that 400 or 800 mg daily over 4 weeks reduced daily cannabis use in men with CUD⁸. This suggests that balancing the THC to CBD ratio of cannabis-based medicines could potentially reduce the development of dependence¹.

Risk vs. benefit

The balance between need and the potential for harm must be always considered for any treatment. Any risk of medicinal cannabis dependence needs to be weighed against alternative medications, some of which may not have been effective, or may have had intolerable side effects, or may have potentially higher problems of abuse, such as opioids. 

The devastating consequences of the prescription opioid crisis are well known. In 2019, nearly 50,000 people in the United States alone died from unintentional opioid-related overdose. People who are dependent on opioids also have an increased risk of premature death due to other complications, reducing lifespan by approximately 15 years⁹.  It has been proposed that the ability of medicinal cannabis to ease this crisis by substituting prescription opioids, may outweigh any negative outcomes¹⁰. Evidence shows that in states of the USA where medicinal cannabis has become legal, there have been reduced rates of opioid prescriptions, opioid abuse, opioid-associated hospital admissions, and overdose mortality rates¹¹ ¹² ¹³

Opioids bind to opioid receptors in a region of the brain that controls breathing. They can therefore stop breathing and heart function in case of overdose¹⁴ ¹⁵.  In contrast, there have been no reported deaths due to overdose from cannabinoids because there are no cannabinoid receptors in brain centres that regulate heart and breathing¹.  Moreover, the levels of cannabinoids needed to induce a potentially fatal overdose would be several orders of magnitude higher than a normal therapeutic dose¹⁷, ¹⁸.

When prescribing THC-containing medications, doctors and patients together need to consider the balance between risk and benefit, particularly when use is likely to be long-term, and discuss the potential risk for dependence and withdrawal as part of the consultation.

How can I reduce the risk of dependence?

Higher doses of THC can increase the risk of dependence, therefore reduce THC dose to less than 10%, or replace with CBD-only formulations, or with full-spectrum products, or with those containing balanced THC and CBD. Higher CBD levels have been shown to improve the dependence-related effects of THC5, 7, 19.  Start with a low dose and increase slowly just until relief of symptoms occur. Lower daily cannabis use is associated with better clinical profiles as well as safer use behaviours, such as preference for CBD and non-inhalation administration routes¹

THC:CBD ratios, frequency of use, routes of administration, and consequent risk of dependence will probably vary between conditions and patients. It also seems likely that individual genetic variations in endocannabinoid system response and metabolism will also affect risk of dependence. 

Finally, studies have found that black market products are not accurately labelled and are inconsistent in their composition², thus carrying a higher risk of dependence.  Therefore, make sure that you are prescribed a legal medicinal cannabis product that comes with a certificate of analysis showing the exact composition of cannabinoids, and that you are monitored regularly by the prescribing medical practitioner. 

For more information, see the TGA’s Guidance for the use of medicinal cannabis in Australia.

NOTE: To reduce the risk of dependence and associated harms, cannabis medicines containing THC are contraindicated for children under the age of 16 years, and for people with a personal history of substance use disorder (abuse, dependence) to alcohol, opioids, benzodiazepines, or illicit stimulants. They are also contraindicated for people with a family or personal history of serious medical or psychiatric conditions including bipolar disorder and psychosis.

  1. Schlag AK, Hindocha C, Zafar R, Nutt DJ, Curran HV. Cannabis based medicines and cannabis dependence: A critical review of issues and evidence. J Psychopharmacol. 2021:269881120986393.
  2. Nutt DJ. Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol. 2003;17(4):355-64.
  3. Carotenuto A, Costabile T, De Lucia M, Moccia M, Falco F, Petruzzo M, et al. Predictors of Nabiximols (Sativex(®)) discontinuation over long-term follow-up: a real-life study. J Neurol. 2020;267(6):1737-43.
  4. Curran HV, Brignell C, Fletcher S, Middleton P, Henry J. Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl). 2002;164(1):61-70.
  5. Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJ, Parsons LH. Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci. 2016;17(5):293-306.
  6. Cannabidiol (CBD). Pre-Review Report. Expert Committee on Drug Dependence. World Health Organization, 39th Meeting, Geneva, 6-7 November 2017. https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf.
  7. Morgan CJ, Freeman TP, Schafer GL, Curran HV. Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology. 2010;35(9):1879-85.
  8. Freeman TP, Hindocha C, Baio G, Shaban NDC, Thomas EM, Astbury D, et al. Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Lancet Psychiatry. 2020.
  9. Lewer D, Jones NR, Hickman M, Nielsen S, Degenhardt L. Life expectancy of people who are dependent on opioids: A cohort study in New South Wales, Australia. J Psychiatr Res. 2020;130:435-40.
  10. Vivace BJ, Sanders AN, Glassman SD, Carreon LY, Laratta JL, Gum JL. Cannabinoids and orthopedic surgery: a systematic review of therapeutic studies. J Orthop Surg Res. 2021;16(1):57.
  11. Shi Y. Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever. Drug Alcohol Depend. 2017;173:144-50.
  12. Shi Y, Liang D, Bao Y, An R, Wallace MS, Grant I. Recreational marijuana legalization and prescription opioids received by Medicaid enrollees. Drug Alcohol Depend. 2019;194:13-9.
  13. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668-73.
  14. Pattinson KT. Opioids and the control of respiration. Br J Anaesth. 2008;100(6):747-58.
  15. White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction. 1999;94(7):961-72.
  16. MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-9.
  17. Gable RS. Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically. Am J Drug Alcohol Abuse. 1993;19(3):263-81.
  18. Lachenmeier DW, Rehm J. Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach. Sci Rep. 2015;5:8126.
  19. Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol. 2013;27(1):19-27.
  20. Gilman JM, Schmitt WA, Wheeler G, Schuster RM, Klawitter J, Sempio C, et al. Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts. JAMA Network Open. 2021;4(4):e215490-e.

Stay up to date

Sign up to the Tetra Health Newsletter