Cannabinoids for Chronic Pain: An Opioid Alternative?
Chronic pain management has become a well-known challenge for psychiatrists and other addiction specialists, partly because almost half of primary care providers (PCPs) are refusing to treat chronic pain in patients, as reported in a recent JAMA Network Open survey. 1 In the face of this PCP response to prescribing opioids, a new challenge is cannabinoid use for analgesia of chronic “benign” pain. The cannabinoids, particularly cannabidiol (CBD), have been hailed as non-addictive solutions to using escalating doses of opioids for chronic pain because cannabinoids potentiate the efficacy and reduce tolerance to opioids, although 10% of people who use tetrahydrocannabinol (THC) become addicted to it. 2,3
This potential for a reduced need for opioids has been further encouraged by early epidemiological data indicating that opioid overdoses and abuse have been significantly lower in states that have legalized cannabinoids. Recent data have cast significant doubt on those early epidemiological data and have instead found opioid overdose rates to be higher in states with legalization of cannabinoids and marijuana. 4 This brief overview focuses on CBD, because data and legal regulation have been rapidly progressing for its potential role in chronic pain management within a PCP setting.
Cannabidiol is the second most prevalent of the active ingredients of cannabis (marijuana), and it is derived directly from the hemp and marijuana plants. While CBD is one of the approximately 100 cannabinoids found in the marijuana plant, by itself CBD does not cause a “high.” 3 The World Health Organization 4 describes it as follows: “In humans, CBD exhibits no effects indicative of any abuse or dependence potential . . . To date, there is no evidence of public health related problems associated with the use of pure CBD.” All 50 states have laws legalizing CBD with varying degrees of restriction, and many people obtain CBD online without a medical cannabis license or physician prescription.
In 2018 the US Congress passed an amendment to the Farm Bill that legalized the growing and production of hemp, which launched a rapidly growing industry for the production of CBD. This legislation initiated FDA action that included legislative hearings about regulation of CBD, which recently began in mid-June 2019. One potential outcome from these hearings will be that regulation of CBD will depend on the dose of CBD. Low-dose CBD may become a nutraceutical, while higher doses will be regulated as a pharmaceutical because of the toxicities of higher dose CBD in producing fatigue and irritability as well as gastrointestinal effects including liver toxicity. In animal models, CBD applied on the skin can help lower pain and inflammation due to arthritis. 5 Another study by Li and colleagues 6 confirmed that CBD inhibits inflammatory and neuropathic pain, two of the most difficult types of chronic pain to treat.
We do not know the most effective therapeutic dose of CBD for most medical conditions including pain, except for two rare seizure disorders: Dravet syndrome and Lennox-Gastaut syndrome. However, some preliminary estimates are available, such as the 5mg/kg twice-daily dose of Epidiolex for these two disorders. 7 Moreover, to compare analgesic effects in a wide range of medications a metric used is the number needed to treat (NNT), with tricyclic antidepressants and opioids having the lowest NNT for treating neuropathic pain (2.6 and 2.1, respectively). 8,9 This means that for every one patient showing a therapeutic response to the treatment agent, the NNT is the number of patients who need to be treated. In other words, for every two patients whose pain is treated with opioids, one will have satisfactory analgesia from chronic neuropathic pain.
The oral CBD spray used in studies have found it to have an NNT of 5.0, which is comparable to many routine agents used in treating neuropathic pain, including SSRIs (NNT 5.0) and gabapentin (NNT 6.4). 10,11 A similar meta-analysis of 18 double-blind, randomized controlled trials on the efficacy of CBD also showed modest cannabinoid analgesia, but also analyzed the harms associated with CBD. They found the number needed to harm (NNH) with CBD, which ideally would be high, ranged from 5 to 8 persons, which is relatively low, and is substantially higher (above 20) for other analgesics. 12-14 Specific adverse events were impaired motor function, NNH=5; altered perception, NNH=7; altered cognitive function, NNH=8. Future studies clearly must assess the efficacy of CBD balanced against the potential for harm in the management of neuropathic pain.
The pharmaceutical industry is well poised to make CBD widely available under various types of individual state level regulation and both with and without prescriptions. The CBD oral solution Epidiolex®, which is available in the US for management of refractory epilepsy, but may offer therapeutic relief to chronic pain conditions as well. The most recent data about Epidiolex report that heroin cue induced craving was significantly reduced in subjects allocated to 400 mg or 800 mg of an oral CBD solution given once daily for three consecutive days. 15 These subjects then were assessed for cue-induced craving and found to have significantly reduced craving for seven days after this treatment. Furthermore, in animals they report that the anti-craving effect may last for five months.
GW pharmaceuticals also produces the drug nabiximols (Sativex®), which is a marijuana extract currently approved in the UK to treat neuropathic pain, such as spasticity, overactive bladder, and other symptoms associated with multiple sclerosis (MS). GW Pharmaceuticals is currently planning to conduct Phase 3 trials for nabiximols in the US. Current investigative drugs developed by Cara Therapeutics (CR701) and Zynerba Pharmaceuticals (ZYN002) are synthetic cannabinoids that show promise to specific neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. 9,16,17
Thus, through exploratory studies in the evolving role of CBD as a therapeutic agent, we can expect greater scientific evidence regarding the potential for cannabinoid alternatives to opioids for chronic analgesia. Whether CBD simultaneously becomes diverted as a potential drug of abuse, however, is a cause for concern and remains to be seen.
Dr Kosten is Professor at the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine and Staff Psychiatrist at Michael E. DeBakey VA Medical Center, Houston, TX. He is on the Editorial Board of Psychiatric Times. Dr Domingo is Assistant Professor at the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX.
This article was originally published on August 8, 2019, and has since been updated. -Ed
1. Lagisetty PA, Healy N, Garpestad C, et al. Access to Primary Care Clinics for Patients With Chronic Pain Receiving Opioids. JAMA Netw Open. 2019;2:e196928.
Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products. Case Summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2.
Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma. Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis’s effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day. Conclusion and Relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.
Program Evaluation of a Home Exercise Program for Chronic Back Pain in the Outpatient Setting
Xiang Jing, DNP and Jamie Lewis, MD
Research indicates many different interventions are potentially therapeutic in managing chronic back pain. While home exercise programs may be cost-effective for individuals, little has been published on the subject of how best to combine functional and psychologic instruments to measure structured exercise programs in an outpatient setting. This DNP project conducted a program evaluation of a pilot project which reviewed the efficacy of a home exercise program for people with chronic back pain. The project was approved by a multi-disciplinary team at a private spine and pain specialty practice. Participants were recruited from patients at this practice, 14 of whom completed this three-month pilot project with no reported adverse events. The program measured participants’ exercise pattern changes, back functional improvement, and compliance to the change of routine through the use of three validated questionnaires: Fear-Avoidance Beliefs Questionnaires (FABQ), Low Back Pain Disability Questionnaire (OSWESTRY), Exercise Self Efficacy Scale (ESES). The program evaluation provided valuable information on how a HEP may further adapt these measurement tools to provide relevant data in a fast-paced outpatient pain management setting.
Interpreting Urine Drug Test Results in the Context of Chronic Opioid Analgesic Therapy and Poppy Seed Consumption
Citation: Jamie Lewis, MD, Karlee De Monnin, BS, Jonathan Smith, BS, Evan Lewis, Marian Wilson, PhD, MPH, RN (12 March 2021). Pain Medicine, pnab082, https://doi.org/10.1093/pm/pnab082
Goalistics Chronic Pain Program
Northwest Spine and Pain Medicine partnered with Washington State University on a research program looking at efficacy of Goalistics Online Pain Program combined with health coaching at treating chronic pain. Validating the effectiveness of Goalistics Chronic Pain Program and other online modalities helps to increase the scope of treatment options readily available to those suffering from chronic pain.
Building Efficacy for Successful Opioid Tapering
It can be challenging to decrease or discontinue opioid pain medication. Northwest Spine and Pain Medicine partnered with Goalistics, LLC to evaluate a new tool to help patients who are undergoing medically supervised opioid tapering. The development and testing of the Building Efficacy for Successful Tapering (BEST) Program is funded by a grant from the National Institute on Drug Abuse. The online BEST Program was designed to:
- Teach pain patients about different methods of pain management that don’t involve pain medication
- Help them to build their own custom list of “pain reducers”
- Allow them to track and test the effectiveness of each method
- Identify the best strategies for them
Two studies were conducted. The first study is a review of the BEST program by patients who are currently undergoing opioid tapering. Their feedback will help ensure that the BEST Program is user-friendly and beneficial to future program users. The second study is a pilot randomized controlled trial to examine the efficacy of the program.
Cannabis use is related to self-efficacy but not sleep or pain symptoms: A survey of adults prescribed opioids for pain or opioid use disorders.
T. Bigand, M. Wilson, S. Riedy, J. Lewis (2017). Cannabis use is related to self-efficacy but not sleep or pain symptoms: A survey of adults prescribed opioids for pain or opioid use disorders [abstract]. The Journal of Pain. 12.121
Inadequate pain management and sleep difficulties are commonly reported by people using opioids to treat persistent pain or for medication-assisted treatment of Opioid Use Disorder (OUD). Cannabis use is frequently reported within both populations to manage pain and sleep problems, although how cannabis influences co-occurring symptoms is uncertain. Self-efficacy, the confidence that one can control symptoms, can improve pain and sleep symptoms. It remains unknown how cannabis use relates to self-efficacy in managing symptoms of pain and sleep. To explore relationships between cannabis use, sleep quality, pain intensity, and self-efficacy, survey data of adults prescribed opioids for OUD (n = 150) and persistent pain (n = 150) were analyzed. The Pittsburgh Sleep Quality Index (PSQI) global score and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity and self-efficacy subscale scores were used to assess sleep quality, pain intensity, and self-efficacy, respectively and a questionnaire assessed cannabis use. Data were analyzed using linear regression with main effects for sample (OUD and persistent pain) and cannabis use (yes/no) in the last month and their interaction. Overall, 87% of all surveyed adults had clinically relevant poor sleep quality (PSQI > 5). Better sleep quality was associated with greater self-efficacy (F1,225 = 23.30, P < .001) and less pain intensity (F1,230 = 29.95, P < .001). Cannabis use in the last month did not predict sleep quality or pain intensity (P > .70). Cannabis users had higher self-efficacy scores than non-users (F1,277 = 6.78, P = .01). Persistent pain patients had poorer sleep quality (F1,225 = 10.14, P = .001) and greater pain intensity (F1,281 = 32.43, P < .001) than OUD patients; self-efficacy did not differ (F1,277 = .27, P = .60). Evidence does not support cannabis for improving pain or sleep for either group, yet cannabis users have more confidence in symptom control. Future studies should focus on interventions that reduce symptom burden while enhancing self-efficacy.