Cannabinoids in the management of difficult to treat pain Opioids for chronic non-cancer pain Efficacy, tolerability and safety of cannabis‐based medicines for chronic pain management – An overview of systematic reviews A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial Cannabis in painful HIV-associated sensory neuropathy Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain Initial experiences with medicinal extracts of cannabis for chronic pain: Results from 34 ‘N of 1’ studies Non-Steroidal Antiinflammatory Drugs as the First Step in Cancer Pain Therapy: Double-blind, Within-Patient Study Comparing Nine Drugs A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. A randomized trial of 2 prescription strategies for opioid treatment of chronic nonmalignant pain. Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy.
This article review s recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms , as well as r and omized clinical trials employing cannabinoids in pain treatment .  Tetrahydrocannabinol ( THC , Marinol ® ) and nabilone ( Cesamet ® ) are currently approved in the United States and other countries , but not for pain indications . Other synthetic cannabinoids , such as ajulemic acid , are in development . Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation . Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC ( partial CB1 receptor agonist ) and cannabidiol ( CBD , a non-euphoriant , anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects ) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis , and in 2007 for intractable cancer pain . Numerous r and omized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain , rheumatoid arthritis and cancer pain . An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006 . Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles . Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise A 36 year old carpenter has a six month history of lower back pain with no specific clinical or radiological findings . As his pain has not responded to paracetamol and non-steroidal anti-inflammatory drugs ( NSAIDs ) , he asks his doctor if he can have “ stronger painkillers ” such as morphine . Opioids are a group of compounds that act by binding to opioid receptors ( μ , κ , and δ ) , which are widely distributed in the brain , spinal cord , and peripheral tissues . They are the mainstay in the management of cancer pain , but published data show a continual increase in the volume of prescribed opioids to manage moderate to severe , chronic , non-cancer pain.1 2 Changes in attitude and aggressive marketing have driven a dramatic increase in use , with more adverse events , including deaths from overdose ( now the second leading cause of accidental death in the US).3 Proponents cl aim that opioids are underused for chronic pain,4 but lack of good scientific data has prevented the formulation of evidence based guidelines for their use , especially in primary care . Several meta-analyses of the effectiveness of opioids have been published . Most of the r and omised clinical trials summarised in these meta-analyses were funded by the pharmaceutical industry and report heterogeneous , short term outcomes in highly selected patients . Non-r and omised and uncontrolled observational studies make up the rest of the literature . Nevertheless , most studies have consistently shown some effectiveness in chronic non-cancer pain by reducing pain intensity . In particular , meta-analyses show the efficacy of opioids in neuropathic pain,5 6 7 although most guidelines regard opioids only as second or third line treatment for such pain because of their risk : benefit profile.8 9 The data are even less encouraging for chronic non-neuropathic pain , the focus of this paper . A 2009 Cochrane review of 10 r and omised or quasi-r and omised controlled trials compared Medicinal cannabis has already entered mainstream medicine in some countries . This systematic review ( SR ) aim ed at evaluating the efficacy , acceptability and safety of cannabis-based medicines for chronic pain management . Qualitative systematic review of SRs of r and omized controlled trials with cannabis-based medicines for chronic pain management . The Cochrane data bases of SRs , Data base of Abstract s of Review s of Effects and PubMed were search ed for SR published in the period January 2009 to January 2017 . Assessment of the method ological quality of SR was performed by the AMSTAR checklist . Out of 748 papers identified , 10 SRs met the inclusion criteria . The method ological quality was high in four and moderate in six SRs . There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis . There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases ( three SRs ) and in cancer pain ( two SRs ) . Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions . It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the st and ard of 21st century clinical care . SIGNIFICANCE We provide an overview of systematic review s on the efficacy , tolerability and safety of cannabis-based medicines for chronic pain management . There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis . There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain CONTEXT Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life . Chemotherapeutic neuropathy responds poorly to conventional treatments , and there is an urgent medical need for new treatments . Recent pre clinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy . OBJECTIVES This was a pilot trial to begin to investigate a currently available cannabinoid agent , nabiximols ( oral mucosal spray containing cannabinoids ) , in the treatment of chemotherapy-induced neuropathic pain . METHODS A r and omized , placebo-controlled crossover pilot study was done in 16 patients with established chemotherapy-induced neuropathic pain . A 0 - 10 point numeric rating scale for pain intensity ( NRS-PI ) was used as the primary outcome measure . RESULTS When examining the whole group , there was no statistically significant difference between the treatment and the placebo groups on the NRS-PI . A responder analysis demonstrated that there were five participants who reported a two-point or greater reduction in pain that trended toward statistical significance and the number needed to treat was five . CONCLUSION Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments . This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five " responders " ( as compared with a decrease of 0.6 with placebo ) and supports that it is worthwhile to study nabiximols in a full r and omized , placebo-controlled trial of chemotherapy-induced neuropathic pain This study compared the efficacy of a tetrahydrocannabinol : cannabidiol ( THC : CBD ) extract , a nonopioid analgesic endocannabinoid system modulator , and a THC extract , with placebo , in relieving pain in patients with advanced cancer . In total , 177 patients with cancer pain , who experienced inadequate analgesia despite chronic opioid dosing , entered a two-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group trial . Patients were r and omized to THC : CBD extract ( n = 60 ) , THC extract ( n = 58 ) , or placebo ( n = 59 ) . The primary analysis of change from baseline in mean pain Numerical Rating Scale ( NRS ) score was statistically significantly in favor of THC : CBD compared with placebo ( improvement of -1.37 vs. -0.69 ) , whereas the THC group showed a nonsignificant change ( -1.01 vs. -0.69 ) . Twice as many patients taking THC : CBD showed a reduction of more than 30 % from baseline pain NRS score when compared with placebo ( 23 [ 43 % ] vs. 12 [ 21 % ] ) . The associated odds ratio was statistically significant , whereas the number of THC group responders was similar to placebo ( 12 [ 23 % ] vs. 12 [ 21 % ] ) and did not reach statistical significance . There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups . No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment . However , the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Question naire showed a worsening in nausea and vomiting with THC : CBD compared with placebo ( P = 0.02 ) , whereas THC had no difference ( P = 1.0 ) . Most drug-related adverse events were mild/moderate in severity . This study shows that THC : CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids UNLABELLED Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain . The safety of cannabis use for medical purpose s has not been systematic ally evaluated . We conducted a prospect i ve cohort study to describe safety issues among individuals with chronic non-cancer pain . A st and ardized herbal cannabis product ( 12.5 % tetrahydrocannabinol ) was dispensed to eligible individuals for a 1-year period ; controls were individuals with chronic pain from the same clinics who were not cannabis users . The primary outcome consisted of serious adverse events and non-serious adverse events . Secondary safety outcomes included pulmonary and neurocognitive function and st and ard hematology , biochemistry , renal , liver , and endocrine function . Secondary efficacy parameters included pain and other symptoms , mood , and quality of life .  Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group ( 141 current users and 58 ex-users ) and 216 controls ( chronic pain but no current cannabis use ) from 7 clinics across Canada . The median daily cannabis dose was 2.5 g/d . There was no difference in risk of serious adverse events ( adjusted incidence rate ratio = 1.08 , 95 % confidence interval = .57 - 2.04 ) between groups . Medical cannabis users were at increased risk of non-serious adverse events ( adjusted incidence rate ratio = 1.73 , 95 % confidence interval = 1.41 - 2.13 ) ; most were mild to moderate . There were no differences in secondary safety assessment s. Quality -controlled herbal cannabis , when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year , appears to have a reasonable safety profile . Longer-term monitoring for functional outcomes is needed . STUDY REGISTRATION The study was registered with www.controlled-trials.com ( IS RCT N19449752 ) . PERSPECTIVE This study evaluated the safety of cannabis use by patients with chronic pain over 1 year . The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day CONTEXT Chronic pain in patients with advanced cancer poses a serious clinical challenge . The Δ9-tetrahydrocannabinol (THC)/cannabidiol ( CBD ) oromucosal spray ( U.S. Adopted Name , nabiximols ; Sativex ( ® ) ) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group . OBJECTIVES This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer . METHODS In total , 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing , who had participated in a previous three-arm ( THC/CBD spray , THC spray , or placebo ) , two-week parent r and omized controlled trial , entered this open-label , multicenter , follow-up study . Patients self-titrated THC/CBD spray ( n=39 ) or THC spray ( n=4 ) to symptom relief or maximum dose and were regularly review ed for safety , tolerability , and evidence of clinical benefit . RESULTS The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for " pain severity " and " worst pain " domains showed a decrease ( i.e. , improvement ) at each visit in the THC/CBD spray patients . Similarly , the European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 scores showed a decrease ( i.e. , improvement ) from baseline in the domains of insomnia , pain , and fatigue . No new safety concerns associated with the extended use of THC/CBD spray arose from this study . CONCLUSION This study showed that the long-term use of THC/CBD spray was generally well tolerated , with no evidence of a loss of effect for the relief of cancer-related pain with long-term use . Furthermore , patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time , suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit Objectives : The objective of this prospect i ve , open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain . Patients and Methods : The primary outcome was the change in the pain symptom score on the S-TOPS ( Treatment Outcomes in Pain Survey — Short Form ) question naire at the 6-month follow-up in an intent-to-treat population . Secondary outcomes included the change in S-TOPS physical , social , and emotional disability scales , the pain severity , and pain interference on the Brief Pain Inventory , sleep problems , and the change in opioid consumption . Results : A total of 274 participants were approved for treatment ; complete baseline data were available for 206 ( intent-to-treat ) , and complete follow-up data for 176 participants . At follow-up , the pain symptom score improved from median 83.3 ( 95 % confidence interval [ CI ] , 79.2 - 87.5 ) to 75.0 ( 95 % CI , 70.8 - 79.2 ) ( P<0.001 ) . The pain severity score ( 7.50 [ 95 % CI , 6.75 - 7.75 ] to 6.25 [ 95 % CI , 5.75 - 6.75 ] ) and the pain interference score ( 8.14 [ 95 % CI , 7.28 - 8.43 ] to 6.71 [ 95 % CI , 6.14 - 7.14 ] ) improved ( both P<0.001 ) , together with most social and emotional disability scores . Opioid consumption at follow-up decreased by 44 % ( P<0.001 ) . Serious adverse effects led to treatment discontinuation in 2 participants . Discussion : The treatment of chronic pain with medicinal cannabis in this open-label , prospect i ve cohort result ed in improved pain and functional outcomes , and a significant reduction in opioid use . Results suggest long-term benefit of cannabis treatment in this group of patients , but the study ’s noncontrolled nature should be considered when extrapolating the results Despite management with opioids and other pain modifying therapies , neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals . Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception . We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV . This was a phase II , double-blind , placebo-controlled , crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy ( DSPN ) . Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes ; they continued on their pre study analgesic regimens throughout the trial . Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting . Treatments were placebo and active cannabis ranging in potency between 1 and 8 % Δ-9-tetrahydrocannabinol , four times daily for 5 consecutive days during each of 2 treatment weeks , separated by a 2-week washout . The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale ( DDS ) from a pretreatment baseline to the end of each treatment week . Secondary measures included assessment s of mood and daily functioning . Of 127 volunteers screened , 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments . Among the completers , pain relief was greater with cannabis than placebo ( median difference in DDS pain intensity change , 3.3 points , effect size=0.60 ; p=0.016 ) . The proportions of subjects achieving at least 30 % pain relief  with cannabis versus placebo were 0.46 ( 95%CI 0.28 , 0.65 ) and 0.18 ( 0.03 , 0.32 ) . Mood and daily functioning improved to a similar extent during both treatment periods . Although most side effects were mild and self-limited , two subjects experienced treatment-limiting toxicities . Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN Objective : To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model . Methods : Prospect i ve r and omized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy . Patients were r and omly assigned to smoke either cannabis ( 3.56 % tetrahydrocannabinol ) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days . Primary outcome measures included ratings of chronic pain and the percentage achieving > 30 % reduction in pain intensity . Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model . Results : Fifty patients completed the entire trial . Smoked cannabis reduced daily pain by 34 % ( median reduction ; IQR = −71 , −16 ) vs 17 % ( IQR = −29 , 8) with placebo ( p = 0.03 ) . Greater than 30 % reduction in pain was reported by 52 % in the cannabis group and by 24 % in the placebo group ( p = 0.04 ) . The first cannabis cigarette reduced chronic pain by a median of 72 % vs 15 % with placebo ( p < 0.001 ) . Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli ( p ≤ 0.05 ) but appeared to have little effect on the painfulness of noxious heat stimulation . No serious adverse events were reported . Conclusion : Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy . The findings are comparable to oral drugs used for chronic neuropathic pain OBJECTIVE To assess the efficacy of Sativex , a cannabis-based medicinal extract , as adjuvant treatment in painful diabetic peripheral neuropathy ( DPN ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial , 30 subjects with painful DPN received daily Sativex or placebo . The primary outcome measure was change in mean daily pain scores , and secondary outcome measures included quality -of-life assessment s. RESULTS There was significant improvement in pain scores in both groups , but mean change between groups was not significant . There were no significant differences in secondary outcome measures . Patients with depression had significantly greater baseline pain scores that improved regardless of intervention . CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN . Depression was a major confounder and may have important implication s for future trials on painful DPN ABSTRACT Background : Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades , possibly accounting for the current opioid addiction epidemic . Co-morbid drug use in those prescribed opioid analgesics is common , but there are few data on polysubstance use patterns . Objective : We explored patterns of use of cigarette , alcohol , and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics .  Methods : We conducted a secondary data analysis of screening interviews conducted as part of a parent r and omized trial of financial incentives to improve HIV outcomes among drug users . In a convenience sample of people with HIV and chronic pain , we collected self-report data on demographic characteristics ; pain ; patterns of opioid analgesic use  ( both prescribed and illicit ) ; cigarette , alcohol , and illicit drug use ( including cannabis , heroin , and cocaine ) within the past 30 days ; and current treatment for drug use and HIV . Results : Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use ( N = 372 , 47.1 % ) . Illicit drug use was common ( N = 505 , 63.9 % ) , and cannabis was the most commonly used illicit substance ( N = 311 , 39.4 % ) . In multivariate analyses , only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use ( adjusted odds ratio = 0.57 ; 95 % confidence interval : 0.38–0.87 ) . Conclusions / Importance : Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management , which could help to address adverse events associated with opioid analgesic use Three Cannabis Based Medicinal Extracts ( CBMEs ) for sublingual use became available in 2000 . A total of 34 ‘ N of 1 ’ studies were undertaken using this novel therapy for patients with chronic , mainly neuropathic , pain and associated symptoms to explore efficacy , tolerability , safety and dosages . Three CBMEs ( Δ9 Tetrahydrocannabinol ( THC ) , Cannabidiol ( CBD ) and a 1 : 1 mixture of them both ) were given over a 12‐week period . After an initial open‐label period , the CBMEs were used in a r and omised , double‐blind , placebo controlled , crossover trial . Extracts which contained THC proved most effective in symptom control . Regimens for the use of the sublingual spray emerged and a wide range of dosing requirements was observed . Side‐effects were common , reflecting a learning curve for both patient and study team . These were generally acceptable and little different to those seen when other psycho‐active agents are used for chronic pain . These initial experiences with CBME open the way to more detailed and extensive studies The efficacy and tolerability of acetylsalicylic acid , paracetamol , diclofenac , ibuprofen , indomethacin , pirprofen , sulindac , naproxen and suprofen were compared in the treatment of cancer pain . In a double-blind , within-patient r and omized study , each drug was given for 1 week to eight patients and for another week to a further eight patients . A total of 65 patients were effectively treated ; only 48 completed week 1 and 41 completed week 2 . Naproxen , diclofenac and indomethacin were highly effective in pain relief ( tested by means of a 100 mm visual analogue scale ) and were relatively well tolerated . It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain UNLABELLED The Food and Drug Administration ( FDA ) , Substance Abuse and Mental Health Services Administration ( SAMHSA ) , and the National Institute for Drug Abuse ( NIDA ) report that no sound scientific studies support the medicinal use of cannabis . Despite this lack of scientific validation , many patients routinely use " medical marijuana , " and in many cases this use is for pain related to nerve injury . We conducted a double-blinded , placebo-controlled , crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain . Thirty-eight patients with central and peripheral neuropathic pain underwent a st and ardized procedure for smoking either high-dose ( 7 % ) , low-dose ( 3.5 % ) , or placebo cannabis . In addition to the primary outcome of pain intensity , secondary outcome measures included evoked pain using heat-pain threshold , sensitivity to light touch , psychoactive side effects , and neuropsychological performance . A mixed linear model demonstrated an analgesic response to smoking cannabis . No effect on evoked pain was seen . Psychoactive effects were minimal and well-tolerated , with some acute cognitive effects , particularly with memory , at higher doses . PERSPECTIVE This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain , and may be an alternative for patients who do not respond to , or can not tolerate , other drugs . However , the use of marijuana as medicine may be limited by its method of administration ( smoking ) and modest acute cognitive effects , particularly at higher doses UNLABELLED The use of opioid medications for treating chronic noncancer pain is growing ; however , there is a lack of good evidence regarding their long-term effectiveness , association with substance abuse , and proper prescribing guidelines . The current study directly compares for the first time in a r and omized trial the effectiveness of a conservative , hold the line ( Stable Dose ) prescribing strategy for opioid medications with a more liberal dose escalation ( Escalating Dose ) approach . This 2-arm , parallel , r and omized pragmatic clinical trial followed 135 patients referred to a specialty pain clinic at a Veterans Affairs Hospital for 12 months ( 94 % male and 74 % with musculoskeletal pain ) . Primary outcomes included monthly or quarterly evaluations of pain severity , pain relief from medications , pain-related functional disability , and opioid misuse behaviors . All subjects received identical pain treatment except for the application of treatment group specific strategies for opioid prescriptions . No group differences were found for primary outcomes of usual pain or functional disability although the Escalating Dose group did show a small but significantly larger increase in self-rated pain relief from medications . About 27 % of patients were discharged over the course of the study due to opioid misuse/noncompliance , but there were no group differences in rate of opioid misuse . PERSPECTIVE The results of this study demonstrate that even in carefully selected patients there is a significant risk of problematic opioid misuse . Although in general there were no statistically significant differences in the primary outcomes between groups , the escalating dose strategy did lead to small improvements in self-reported acute relief from medications without an increase in opioid misuse , compared to the stable dose strategy UNLABELLED We assessed the efficacy of dronabinol ( Marinol capsules ; Solvay Pharmaceuticals , Brussels , Belgium ) , a synthetic Delta(9)-THC ( tetrahydrocannabinol ) , in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment . Phase I of this 2-phase study was a r and omized , single-dose , double-blinded , placebo-controlled , crossover trial in which subjects were r and omly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three , 8-hour visits . Baseline self-report measures , hourly ratings of pain intensity , pain relief , pain bothersomeness , treatment satisfaction , mood , side effects , and blood serum levels were obtained . Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids . Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo . No differences in benefit were found between the 20 mg and 10 mg doses . In the Phase II trial , titrated dronabinol contributed to significant relief of pain , reduced pain bothersomeness , and increased satisfaction compared with baseline . The incidence of side effects was dose-related . Overall , the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain . PERSPECTIVE This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids . The results of our preliminary study suggest that dronabinol , a synthetic THC , may have an additive effect on pain relief
There was an increased risk of non-serious AEs with cannabinoids compared with placebo .
Conclusions There was moderate evidence to support cannabinoids in treating chronic , non-cancer pain at 2 weeks .
Similar results were observed at later time points , but the confidence in effect is low .
There is little evidence that cannabinoids increase the risk of experiencing serious AEs , although non-serious AEs may be common in the short-term period following use
Background For patients with chronic , non-cancer pain , traditional pain-relieving medications include opioids , which have shown benefits but are associated with increased risks of addiction and adverse effects .
Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of r and omized clinical trials in recent years ; therefore , a systematic review of the evidence was warranted .
Objective To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic , non-cancer-related pain .