A 59-year-old White man from South Carolina, accompanied by his wife, presented to the ReLeaf Institute in Los Angeles for evaluation. For the past 12 years, he had been receiving opioid-based pain management for degenerative disk disease and a herniated disk. He reported tingling in the hands and buttocks with pain focused in the coccyx and lower back, which he said ‘felt like a horse was biting him’.
The patient’s self-reported pain scores ranged from 6 to 7 on “good” days to 9 to 10 on “worst” days (0–10 visual analog scale). During the intake interview, the patient expressed frustration, saying he felt “abandoned” by his physician and fearful of opioid withdrawal and increased pain severity based on previous unsuccessful attempts at discontinuation. The patient reported being forced to stop all opioids by his prescribing physician in the next few months.
The patient’s past medical history was significant for, asthma, allergies (including penicillin, sulfa, theophylline, urinol, and shrimp), gastroesophageal reflux disease, dysphagia, hemorrhoids, post-traumatic stress disorder, anxiety, seasonal affective disorder, and erectile dysfunction. In addition to his degenerative disc disease, his musculoskeletal history included, 3 knee surgeries, a clavicle fracture, and a dislocated shoulder. He reported no history of recreational drug, alcohol, or tobacco use.
Although the patient resided in South Carolina, he secured a short-term rental in Los Angeles. He was on medical disability from work due to low back pain. A review of the patient’s medications was notable for 180 morphine milligram equivalent (MME) opioids per day. (Table 1 presents the patient’s complete medication list.) He had been receiving this specific dose for 12 years.
Physical examination revealed a generally well-appearing, but anxious man with sweaty palms carrying a backpack containing his medications (he carried them everywhere). He was 1.82 m tall and weighed 103.4 kg (body mass index 29.3 kg/m2). Vital signs were stable on initial evaluation. He had normal ambulation and used an orthopedic coccyx seat cushion to alleviate pain while sitting. The remainder of the examination was unremarkable.
The patient was started on opioid substitution therapy involving a combination of cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) tincture, commonly referred to as high-ratio CBD-to-THC, with an additional, as-needed THC-only chocolate edible. This protocol was based on previous clinical patient experiences and published literature.1-4 The patient did not meet California state requirements for medical cannabis due to his status as a non-California resident.)
Cannabis products were obtained from a licensed recreational dispensary. The patient was placed under the care of a local family physician, who managed the patient’s pharmaceutical medications throughout the treatment period.
The cannabis substitution therapy, created and designed by Dr. Yafai) was CBD ~23 mg plus THC ~6 mg oil (minor cannabinoids: 0.4 mg tetrahydrocannabinolic acid [THCA], 1.2 mg cannabidiolic acid [CBDA], 0.06 mg cannabinol [CBN]; negligible cannabinoids, terpenes, and flavonoids were not labeled/measured in these products). At the initiation of treatment, the patient was instructed to take the CBD:THC oil sublingually with meals 3 times daily.
He was also prescribed a topical pomade of CBD 150 mg per ounce to be used as needed (Table 2). He was permitted to take an additional 5 to 10 mg THC chocolate every 4 hours during active withdrawal periods as needed (maximum dose, 60 mg/d THC). This dose was initiated based on the patient’s preexisting tolerance to high-dose opioids. It does not represent a typical starting dose and is not recommended for chronic pain in opioid-naive patients.
After the patient’s first dose of CBD:THC oil (to determine his tolerance, safety, and comfort with cannabis), he decreased opioids, alprazolam, and meloxicam (Table 2). During 7 days of treatment, there was a 50% decrease in oxycodone/acetaminophen 10/325 mg (but not oxycodone 10 mg), a 33% decrease in alprazolam, and a 50% decrease in meloxicam without any symptoms of opioid withdrawal (eg, diarrhea, vomiting, shakes).
Sweating, anxiety, and irritability associated with previous opioid and alprazolam use improved. Notably, during the first 7 days of cannabis substitution therapy, the patient felt well enough to decrease alprazolam from two-thirds of a tablet to half, resulting in increased light and sound sensitivity. The patient’s self-reported pain score was 4 out of 10, representing a 30% decrease in pain while decreasing opioid doses. (Table 2 presents cannabis substitution details.)
Toward the end of the treatment plan, the patient unexpectedly discontinued cannabis substitution therapy for 5 days (4/1/18–4/6/18) due to a self-perceived allergic reaction. This abrupt cessation resulted in the immediate onset of pain, diarrhea, vomiting, and insomnia—symptoms consistent with acute opioid withdrawal5 that were noticeably absent when he was on cannabis substitution therapy. He became severely dehydrated and required home health involvement and IV fluids. Symptoms resolved after the patient restarted cannabis substitution therapy. This was the only time during treatment that the patient experienced vomiting, diarrhea, increased pain, and insomnia.
At the end of opioid cessation (0 MME), the patient began tapering off cannabis substitution therapy to achieve the final goal of zero cannabis products before returning to South Carolina. On day 15 of opioid cessation, he began titrating down CBT:THC oil to twice daily. Overall, his sensitivity to light and sound improved. Moreover, there was a substantial reduction in pain intensity. His dysphagia resolved, bowel movements were normal, and erectile dysfunction improved with increased libido and daily erections. (Table 1 provides the patient’s medication list at the end of treatment, and Table 3 immediate and delayed side effects.)
In 21 days (5/1/18), the patient decreased routine cannabis oils and was limited to 32 mg THC chocolate as needed and 2.8 mg CBD plus 2.8 mg THC spray once daily. After an additional 14 days, that patient discontinued all cannabis products and returned home, free of opioids, no cannabis, and no withdrawal symptoms.
The United States has an epidemic of opioid dependency and deaths due to prescription and illicit opioids.6 Opioid-related death is now the second leading cause of accidental death in the United States, which has been associated with an overall decrease in life expectancy.7 Given these lethal outcomes, researchers and physicians have sought alternative forms of pain management.8
Opioids work by binding to and activating μ receptors, which are located throughout the body. Discontinuing opioid medications can precipitate withdrawal symptoms, preventing patients from stopping these medications on their own. Patients with opioid addiction or dependence can seek treatment in an in- or outpatient setting to evaluate and treat withdrawal symptoms such as diarrhea, vomiting, sweats, and pain.3 Often, treatments use other opioid agonists or antagonists, further complicating efforts to become opioid-free.
Current research has shown a 25% decrease in opioid-related deaths associated with legalized medical cannabis laws, further improving with the opening of a dispensary.9 There has also been a surge in the public perception and self-reports that cannabis (nonspecific to the chemical components) can help with opioid withdrawal.
In the current medical climate, there are mandates to reduce the number of opioid prescriptions. To limit opioid use, some physicians notify patients that after a short duration of treatment, they will decrease their opioid prescriptions. Unfortunately, this method has proved problematic, leaving many patients in worse pain and withdrawal.10-12
Cannabinoids derived from Cannabis Sativa L are widely available – medically in 38 states and recreationally in 23 states and Washington, DC. Whereas THC is psychoactive and can be addictive,4 non-THC cannabinoids are believed to be relatively non-psychoactive and well tolerated. Researchers are investigating cannabinoids, specifically CBD, as a harm-reduction pathway for patients with opioid addiction due to their favorable safety profile.1,8,9
It is important to stress that patients who wish to decrease or discontinue opioid use via cannabis substitution therapy must be monitored under close medical supervision. Cannabis is available in variable concentrations, ratios, and dosages. In particular, dosing THC without the assistance of a trained physician may result in serious health consequences. Excessive or accidental overuse/misuse of THC can cause temporary nausea, vomiting, panic attacks, tachycardia, hypotension, vertigo, and altered speech and/or thoughts that can lead to emergency department visits.
Combining cannabis-based medications with opioids can increase the activity of the opioid and should be monitored closely.1,2 It is essential that physicians are educated on cannabis medicine, especially those managing chronic pain patients with opioids in states where cannabis is medically and/or recreationally available.
One challenge during treatment was the disconnect between what was recommended by the physician and what the patient received at the dispensary. The budtender sold the patient a vape pen, advising him that it was the same as the oil tinctures being used. This issue highlights the need for improved communication between medical dispensaries/budtenders and physicians and the need to educate and train dispensary employees.
At the end of cannabis substitution therapy, after discontinuing opioids, this patient was in less pain than at the initial presentation. Opioid-induced hyperalgesia (OIH), the sensitization of pain receptors associated with opioid use,13-16 has been documented in the literature. OIH is a plausible explanation for the patient’s pain improvement with the cessation of opioids. Examining the patient’s comorbid complaints also points to opioids as the cause of thermoregulatory dysfunction17 and “hot flashes,” which also subsided after he discontinued opioids. The anti-inflammatory properties and analgesic effects of cannabinoids described in the literature18-21 could also have contributed to the patient’s decreased pain at the end of treatment.
Cannabis is a Schedule I drug, limiting its clinical research. Yet in 2017, the U.S. National Academies of Sciences, Engineering, and Medicine reviewed available data and concluded that “substantial evidence” supports using cannabis for chronic pain symptoms.22 Cannabis also has the potential to reduce the amount of opioids taken.22
One study showed that the emergence of medical cannabis dispensaries in the United States has resulted in a decline in opioid prescriptions and related costs.23 Another study found that the legalization of medical cannabis was positively associated with a 23% decrease in hospitalizations and a 13% decrease in overdoses caused by opioids.24 Additionally, a study evaluating Medicare Part D (2010–2013) showed a decline in the use of pain medication after the introduction of medical cannabis laws.25
Given the widely accepted addictive potential, adverse side effects and high morbidity rate associated with prescription opioids, their use should be limited and temporary as is standard medical practice in most other countries. Cannabis substitution therapy offers a non–opioid-based approach for patients with chronic pain who seek to discontinue opioids without experiencing withdrawal symptoms.
This case demonstrates the effectiveness of cannabis substitution therapy using a combination of orally dosed CBD:THC tinctures and THC based edibles to safely and rapidly detoxify a patient off prescription opioids. It is imperative that the medical community embrace cannabis education programs, emerging polices, and endorse the therapeutic use of cannabinoids as complement to conventional medical treatments.
I look forward to advancing the field of cannabis medicine, especially as it relates to reducing opioid use.
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Dr. Yafai has no financial conflicts of interest to disclose.
The author acknowledges the patient discussed in this case report as well as Amy Mikail-Wolf, MD; Natalie Voskanian Davis, MD; and Belinda Tam, MD, PHD, for their contributions to this case report.
- Hurd YL, Yoon M, Manini AF, et al. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. 2015;12(4):807-815.
- Hurd YL, Spriggs S, Alishayev J, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-bind randomized placebo-controlled trial. Am J Psychiatry. 2019;176(11):911-922.
- Apgar L. Opioid wean with medical cannabis: a case report. 2020;2(1):22-24.
- Shaw C, Marcu J. Case report: cannabidiol in the management of acute opioid withdrawal. 2021;3(1):6-11.
- Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). J Psychoactive Drugs. 2003;35(2):253-259.
- Mendelson J, Flower K, Pletcher MJ, Galloway GP. Addiction to prescription opioids: characteristics of the emerging epidemic and treatment with buprenorphine. Exp Clin Psychopharmacology. 2008;16(5):435-441.
- American Academy of Family Physicians. CDC data show U.S. Life expectancy continues to decline. Accessed July 15, 202. https://www.aafp.org/news/health-of-the-public/20181210lifeexpectdrop.html
- Lucas P, Reiman A, Earleywine M, et al. Cannabis as a substitute for alcohol and other drugs: a dispensary-based survey of substitution effect in Canadian medical cannabis patients. Addiction Res Ther. 2013;21(5):435-442
- 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):1668-1673.
- Ziegler SJ. The proliferation of dosage thresholds in opioid prescribing policies and their potential to increase pain and opioid-related mortality. Pain Med. 2015;16(10):1851-1856.
- Rubin R. Limits on opioid prescribing leave patients with chronic pain vulnerable. 2019;321(21):2059-2062.
- Chua KP, Brummett CM, Waljee JF. Opioid prescribing limits for acute pain: potential problems with design and implementation. 2019;321(7):643-644.
- Mitra S. Opioid-induced hyperalgesia: pathophysiology and clinical implications. J Opioid Manag. 2008;4(3):123-130.
- Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161.
- Higgins C, Smith BH, Matthews K. Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis. Br J Anaesth. 2019;122(6):e114-e126.
- Youssef F, Pater A, Shehata M. Opioid-induced hyperalgesia. J Pain Relief. 2015;4:183.
- Adler MW, Geller EB, Rosow CE, Cochin J. The opioid system and temperature regulation. Annu Rev Pharmacol Toxicol. 1988;28:429-449.
- Nagarkatti PS, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-1349.
- Perrot S. Cannabis: the analgesic and antiinflammatory medication of the future? Joint Bone Spine. 2004;71(1):7-8.
- Moretti S, Castelli M, Franchi S, et al. Δ9‐Tetrahydrocannabinol‐induced anti‐inflammatory responses in adolescent mice switch to proinflammatory in adulthood. J Leukoc Biol. 2014;96(4):523-534.
- Formukong EA, Evans AT, Evans FJ. Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. 1988;12(4):361-371.
- Reiman A, Welty M, Solomon P. Cannabis as a substitute for opioid-based pain medication: patient self-report. Cannabis Cannabinoid Res. 2017;2(1):160-166.
- Volkow ND, Baler RD, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219-2227.
- Shi Y. Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever. Drug Alcohol Depend. 2017;173:144-150.
- Bradford AC, Bradford WD. Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D. Health Aff (Millwood). 2016;35(7):1230-1236.