humulene and Neuralgia

As far as 80% of people diagnosed with multiple sclerosis (MS) experience disabling symptoms in the course of the disease, such as spasticity and neuropathic pain. As first-line symptomatic therapy is associated with important adverse reactions, cannabinoids have become increasingly popular among patients with MS. This review intends to provide an overview of the evidence of the role of cannabinoids in treating symptoms related to MS and to encourage further research on this matter.. To date, the evidence supporting the role of cannabis and its derivatives in alleviating the MS-related symptoms comes only from studies on experimental models of demyelination. To the best of our knowledge, relatively few clinical trials inquired about the therapeutic effects of cannabinoids on patients with MS, with variable results.. We conducted a literature search through PubMed and Google Scholar from the beginning until 2022. We included articles in English describing the latest findings regarding the endocannabinoid system, the pharmacology of cannabinoids, and their therapeutic purpose in MS.. Evidence from preclinical studies showed that cannabinoids can limit the demyelination process, promote remyelination, and have anti-inflammatory properties by reducing immune cell infiltration of the central nervous system in mice with experimental autoimmune encephalomyelitis. Moreover, it has been established that experimental autoimmune encephalomyelitis mice treated with cannabinoids experienced a significant reduction of symptoms and slowing of the disease progression. Given the complexity of human immune and nervous systems, cannabinoids did not have the anticipated effects on human subjects. However, data obtained from clinical trials showed some beneficial results of cannabinoids as a single or as add-on therapy in reducing the spasticity and pain related to MS.. Considering their various mechanisms of action and good tolerability, cannabinoids remain an interesting therapy for spasticity and chronic pain related to MS.

Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Models, Theoretical; Multiple Sclerosis; Muscle Spasticity; Neuralgia

The naturally occurring cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPM) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products' growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients.

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabis; Facial Pain; Humans; Inflammation; Neuralgia

Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required.. To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS.. We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews.. We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS.. We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence.. We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female.  The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I. Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.

Topics: Activities of Daily Living; Adolescent; Adult; Analgesics; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Plant Extracts; Quality of Life; Young Adult

Products derived from the plant

Topics: Analgesics; Animals; Canada; Cannabis; Chronic Pain; Europe; Humans; Medical Marijuana; Neuralgia; Pain Management

The high prevalence of inadequately managed chronic pain indicates the need for alternative and multimodal treatment options. Use of cannabinoids in medicine is becoming a growing area of interest, specifically in the context of chronic pain. The efficacy of cannabinoids for the treatment of chronic pain is not well established.. The objectives of this rapid systematic literature review are to summarize the efficacy and secondary effects of cannabinoids for chronic pain management.. Rapid systematic review of randomized control trials.. Individuals with chronic pain (n = 1352).. Embase, Cochrane, PubMed, and CINAHL databases were searched. Inclusion criteria included cannabis of any formulation used to treat chronic pain of any origin.. Thirteen randomized controlled trials met the inclusion criteria. Five demonstrated moderate analgesic effects of cannabis for chronic pain, and eight concluded there were no significant impacts on pain in the cannabis-treated group versus the control group.. Evidence on the efficacy of cannabinoids for chronic pain shows patient-perceived benefit but inconsistent other treatment effects. These findings indicate cannabinoids may have a modest analgesic effect for chronic neuropathic pain conditions, and that the use of cannabinoids is relatively safe, with few severe adverse events. This review concludes that cannabinoids may have a potential role in chronic pain management. Inconsistent evidence on the efficacy of cannabis to treat chronic pain indicates the need for more studies on a larger scale. Clinicians should draw on available evidence and consider cannabinoids as a potential approach to chronic pain management.

Topics: Analgesics; Cannabinoids; Cannabis; Chronic Pain; Humans; Neuralgia

We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

Topics: Analgesics; Animals; Cannabinoids; Cannabis; Endocannabinoids; Male; Models, Animal; Neuralgia

Cannabis has been shown to be beneficial in the treatment of pain and inflammatory diseases. The biological effect of cannabis is mainly attributed to two major cannabinoids, tetrahydrocannabinol and cannabidiol. In the majority of studies to-date, a purified tetrahydrocannabinol and cannabidiol alone or in combination have been extensively examined in many studies for the treatment of numerous disorders including pain and inflammation. However, few studies have investigated the biological benefits of full-spectrum cannabis plant extract. Given that cannabis is known to generate a large number of cannabinoids along with numerous other biologically relevant products including terpenes, studies involving purified tetrahydrocannabinol and/or cannabidiol do not consider the potential biological benefits of the full-spectrum cannabis extracts. This may be especially true in the case of cannabis as a potential treatment of pain and inflammation. Herein, we review the pre-clinical physiological and molecular mechanisms in biological systems that are affected by cannabis.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Humans; Inflammation; Neuralgia; Plant Extracts

Medicinal use of

Topics: Alzheimer Disease; Anxiety; Bicyclic Monoterpenes; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Cognitive Dysfunction; Dronabinol; Humans; Inflammatory Bowel Diseases; Neuralgia; Neuroprotective Agents; Nootropic Agents; Schizophrenia; Sesquiterpenes; Terpenes

Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain. The benefits of cannabis are mediated largely by cannabinoids, the most prominent of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). As such, THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation. While a plethora of studies have examined the biochemical effects of purified THC and/or CBD, only a few have focused on the effects of full-spectrum cannabis plant extract. Accordingly, studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts. Indeed, the cannabis plant produces a wide range of cannabinoids, terpenes, flavonoids, and other bioactive molecules which are likely to contribute to the different biological effects. The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis.. Literature review was performed to further understand the effect of clinically used full-spectrum cannabis extract in patients with multiple sclerosis.. Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.

Topics: Analgesics; Anti-Inflammatory Agents; Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Neuralgia; Plant Extracts

Despite the fact that the risk versus benefit of smoking cannabis has not been extensively studied, many individuals with multiple sclerosis are smoking cannabis to reduce their pain intensity and spasticity. The lack of information about inhaled cannabis might be attributed to the fact that most trials focus on orally administered cannabis. Given the fact that the administration of cannabis via inhalation is known to rapidly deliver cannabinoids with a higher total bioavailability than what can be achieved through oral or buccal routes, it is important to understand the clinical trials conducted using smoked cannabis on patients with multiple sclerosis.. We sought to discuss the relevant literature about the safety and efficacy of smoked cannabis in multiple sclerosis patients in order to further understand the risks and benefits of this potential therapy for this patient population.. The current knowledge about the potential effects of smoked cannabis on treating neuropathic pain associated with multiple sclerosis is reviewed. In addition, we discuss the possible adverse effects associated with smoking cannabis and we suggest safer as well as new effective inhaled cannabis formulations for the treatment of neuropathic pain associated with multiple sclerosis.

Topics: Administration, Inhalation; Cannabis; Cognitive Dysfunction; Humans; Marijuana Smoking; Medical Marijuana; Multiple Sclerosis; Neuralgia

The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.. This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.. A systematic review and meta-analysis.. An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.. The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.. Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.. The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.

Topics: Cannabidiol; Cannabis; Chronic Pain; Dronabinol; Drug Combinations; Humans; Medical Marijuana; Neuralgia; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Treatment Outcome

Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.

Topics: Animals; Antineoplastic Agents; Cannabinoids; Cannabis; Humans; Nausea; Neoplasms; Neuralgia; Vomiting

To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications.. In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events.. An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects.. There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.

Topics: Analgesics; Cannabis; Chronic Pain; Drug Therapy, Combination; Humans; Medical Marijuana; Neuralgia; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic

The treatment of pain, particularly neuropathic pain, is one of the therapeutic applications of cannabis and cannabinoids that is currently under investigation and that stimulates interest among clinicians and basic researchers. Animal pain models, including models of acute, antinociceptive, inflammatory and neuropathic pain, have demonstrated the antinociceptive efficacy of cannabinoids without causing serious alterations in animal behaviour. These data, together with the historic and current empiric use of cannabinoids, support the interest in the analysis of their effectiveness in treating neuropathic pain. The evaluation of controlled trials that focus on the effect of cannabinoids on neuropathic pain reveals that this class of drugs is able to significantly reduce pain perception. Nevertheless, this effect is generally weak and clinical relevance remains under evaluation. Moreover, there is a lack of controlled trials and, in particular, comparisons with other drugs generally used in the treatment of neuropathic pain. Despite the fact that further research is required to achieve a definitive assessment, current data obtained from basic research and from analysis of the available controlled trials indicate that cannabinoids can be accepted as a useful option in the treatment of neuropathic pain.

Topics: Animals; Cannabinoids; Cannabis; Humans; Neuralgia; Pain Measurement; Receptors, Cannabinoid

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain.. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning.

Topics: Administration, Inhalation; Adult; Affect; Cannabis; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Humans; Hyperalgesia; Linear Models; Male; Middle Aged; Neuralgia; Neuropsychological Tests; Pain Measurement; Pain Threshold; Patient Selection; Phytotherapy; Socioeconomic Factors; Treatment Outcome; Volatilization

Topics: Animals; Cannabidiol; Cannabis; Mice; Microglia; Neuralgia; Neuroinflammatory Diseases; Oils; Quality of Life; Receptor, Cannabinoid, CB2

Although cannabis has become an increasingly common method for pain management among people with multiple sclerosis (PwMS), there is a dearth of knowledge regarding the types of cannabis products used as well as the characteristics of cannabis users. The current study aimed to (1) describe the prevalence of cannabis use and the routes of administration of cannabis products in adults with an existing chronic pain condition and MS, (2) to examine differences in demographic and disease-related variables between cannabis users and non-users, and (3) to examine differences between cannabis users and non-users in pain-related variables, including pain intensity, pain interference, neuropathic pain, pain medication use, and pain-related coping.. Secondary analysis of baseline data from participants with multiple sclerosis (MS) and chronic pain (N = 242) enrolled in an RCT comparing mindfulness-based cognitive therapy (MBCT), cognitive-behavioral therapy (CBT), and usual care for chronic pain. Statistical methods included t-tests, Mann-Whitney tests, chi-square tests, and Fisher's exact tests to assess for differences in demographic, disease-related, and pain-related variables between cannabis users and non-users.. The current study identified factors that may intersect with cannabis use for pain management and adds to our current knowledge of the types of cannabis products used by PwMS. Future research should continue to investigate trends in cannabis use for pain management, especially as the legality and availability of products continue to shift. Additionally, longitudinal studies are needed to examine the effects of cannabis use on pain-related outcomes over time.

Topics: Adult; Cannabis; Chronic Pain; Humans; Medical Marijuana; Middle Aged; Multiple Sclerosis; Neuralgia

Neuropathic pain and other pain disorders have received attention as potential indications for use of cannabis-based medicines or medical cannabis (CBM/MC). Evidence regarding the efficacy and safety of CBM/MC for pain disorders is, however, insufficient. Denmark introduced a pilot programme of medical cannabis in January 2018. We aimed to evaluate efficacy, safety, and non-specific effects of CBM/MC used under the pilot programme compared with controls.. We conducted a nationwide register-based cohort study in Denmark, identifying all individuals redeeming at least one prescription for CBM/MC for either neuropathic pain (n = 1817) or other and unspecified pain disorders (n = 924), and to match one control to each case using propensity score matching.. Among both patient groups, users of THC used more opioids during follow-up than controls. Among patients with neuropathic pain, however, users of either CBD, THC, or combined CBD + THC used less gabapentin than controls. Users of all three classes of CBM/MC were hospitalized fewer days than controls among neuropathic-pain patients but not among patients with other or unspecified pain disorders.. CBM/MC were generally safe and even displayed some positive effects among patients with neuropathic pain. We conclude that CBM/MC are safe and possibly efficacious for patients with neuropathic pain but not patients with other pain disorders.. Patients with neuropathic pain may benefit from treatment with cannabis-based medicines or medical cannabis (CBM/MC), particularly in terms of reduced use of gabapentin and fewer days admitted to hospitals, compared with propensity score matched controls. CBM/MC did not, however, reduce the use of opioids. We did not find evidence that CBM/MC were effective for patients with other pain disorders.

Topics: Cannabis; Cohort Studies; Humans; Medical Marijuana; Neuralgia; Propensity Score

(1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination. (2) Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain. (3) Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630. (4) Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.

Topics: Analgesics; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Disease Models, Animal; Dronabinol; Hallucinogens; Hyperalgesia; Mice; Neuralgia

(1) Background: Recently, a number of side chain length variants for tetrahydrocannabinol and cannabidiol have been identified in cannabis; however, the precursor to these molecules would be based upon cannabigerol (CBG). Because CBG, and its side chain variants, are rapidly converted to other cannabinoids in the plant, there are typically only small amounts in plant extracts, thus prohibiting investigations related to CBG and CBG variant therapeutic effects. (2) Methods: To overcome this, we developed an efficient synthesis of corresponding resorcinol fragments using the Wittig reaction which, under acid catalyzed coupling with geraniol, produced the desired side chain variants of CBG. These compounds were then tested in an animal model of chemotherapeutic-induced neuropathic pain and to reduce colorectal cancer cell viability. (3) Results: We found that all side-chain variants were similarly capable of reducing neuropathic pain in mice at a dose of 10 mg/kg. However, the molecules with shorter side chains (i.e., CBGV and CBGB) were better at reducing colorectal cancer cell viability. (4) Conclusions: The novel synthesis method developed here will be of utility for studying other side chain derivatives of minor cannabinoids such as cannabichromene, cannabinol, and cannabielsoin.

Topics: Animals; Cannabinoids; Cannabis; Colorectal Neoplasms; Dronabinol; Mice; Neuralgia

Cannabis related online searches are associated with positive attitudes toward medical cannabis, particularly when information is obtained from dispensaries. Since pain is the main reason for medicinal cannabis use, information from dispensary websites has the potential to shape the attitude of pain patients towards cannabis. This is relevant because cannabis has demonstrated efficacy in neuropathic pain with low tetrahydrocannabinol (THC) concentrations (< 5-10%), in contrast to potent cannabis (>15% THC), which is highly rewarded in the recreational realm. The role of CBD in pain is not clear, however it has gained popularity. Thus, we hypothesize that the potency of medical cannabis that is advertised online is similar to the cannabis advertised for recreational purposes, which would potentially create a misconception towards medical cannabis. The current lack of knowledge surrounding advertised potencies in the legal cannabis market limits the ability to generate clear policies regarding online advertising to protect patients that are willing to use cannabis for their condition. Thus, we evaluated the advertised THC and CBD content of cannabis products offered online in dispensaries in the United States to determine products' suitability to medicinal use and compare the strength of products offered in legal medical and recreational programs. We recorded THC and CBD concentrations for all herb cannabis products provided by dispensary websites and compared them between or within states. Four Western states (CA, CO, NM, WA) and five Northeastern states (ME, MA, NH, RI, VT) were included. A total of 8,505 cannabis products across 653 dispensaries were sampled. Despite the clear differences between medicinal and recreational uses of cannabis, the average THC concentration advertised online in medicinal programs was similar (19.2% ±6.2) to recreational programs (21.5% ±6.0) when compared between states with different programs, or between medicinal and recreational programs within the same states (CO or WA). Lower CBD concentrations accompanied higher THC products. The majority of products, regardless of medicinal or recreational programs, were advertised to have >15% THC (70.3% - 91.4% of products). These stated concentrations seem unsuitable for medicinal purposes, particularly for patients with chronic neuropathic pain. Therefore, this information could induce the misconception that high potency cannabis is safe to treat pain. This data is consistent with

Topics: Analgesics; Cannabis; Dronabinol; Drug-Related Side Effects and Adverse Reactions; Humans; Illicit Drugs; Medical Marijuana; Neuralgia; United States

A descriptive qualitative study.. To explore why individuals with spinal cord injury (SCI) choose to use cannabis to manage their pain and their experiences in doing so.. Community-dwelling adults with SCI in New Zealand.. Semi-structured interviews were conducted with individuals who had a SCI, experienced pain, and self-reported use of cannabis to manage their pain. Interviews were recorded, transcribed, and subject to thematic analysis.. Eight individuals participated in this study. We interpreted six themes that captured the participants' perspectives regarding their choice to, and perceptions of, using cannabis to manage SCI pain. Participants were motivated to use cannabis when other pain management strategies had been ineffective and were well-informed, knowledgeable cannabis consumers. Participants reported cannabis reduced their pain quickly and enabled them to engage in activities of daily living and participate in life roles without the drowsiness of traditional prescribed pain medication. Despite the positive aspects, participants were concerned about the irregularity of supply and inconsistent dosage.. Findings show that cannabis is used to reduce pain after SCI and enable increased community participation. Findings suggest that future studies examining the efficacy of cannabinoids in managing pain include function and participation outcome measures rather than solely focusing on measuring pain intensity. Focusing on meaningful outcomes may contribute to a greater understanding of the experiences of people with SCI.

Topics: Adult; Cannabis; Female; Humans; Male; Middle Aged; Neuralgia; New Zealand; Pain Management; Qualitative Research; Self Medication; Spinal Cord Injuries; Surveys and Questionnaires; Young Adult

Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/β-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.

Topics: Animals; Cannabinoids; Cannabis; Cell Line, Tumor; Cell Proliferation; Humans; Neuralgia; Plant Leaves; Wnt Signaling Pathway

Topics: Cannabis; Chronic Pain; Humans; Medical Marijuana; Neuralgia

Topics: Cannabis; Chronic Pain; Humans; Neuralgia; Pain Management

Topics: Cannabinoids; Cannabis; Humans; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Nausea; Neuralgia; Vomiting

Cannabis-based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis-based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis-based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis-based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline-recommended first- and second-line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non-neuropathic noncancer pain), the use of cannabis-based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis-based medicines should be terminated.. This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis-based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients.

Topics: Cannabis; Chronic Pain; Europe; Humans; Medical Marijuana; Neuralgia; Pain Management

Topics: Analgesics, Opioid; Cannabinoids; Cannabis; Chronic Pain; Humans; Neuralgia

Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain, however, this is hampered by their side effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy, and sedation. Cannabidiol produced a lesser dose-dependent reduction in allodynia, but did not produce the cannabinoid side effects. When co-administered in a fixed ratio, THC and CBD produced a biphasic dose-dependent reduction in allodynia. At low doses, the THC:CBD combination displayed a 200-fold increase in anti-allodynic potency, but had lower efficacy compared with that predicted for an additive drug interaction. By contrast, high THC:CBD doses had lower potency, but greater anti-allodynic efficacy compared with that predicted for an additive interaction. Only the high dose THC:CBD anti-allodynia was associated with cannabinoid side effects and these were similar to those of THC alone. Unlike THC, the low dose THC:CBD anti-allodynia was not cannabinoid receptor mediated. These findings demonstrate that CBD synergistically enhances the pain-relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side effects. This suggests that low dose THC:CBD combination treatment has potential in the treatment of neuropathic pain.

Topics: Analgesics; Animals; Cannabidiol; Cannabis; Disease Models, Animal; Dose-Response Relationship, Drug; Dronabinol; Hyperalgesia; Male; Mice, Inbred C57BL; Neuralgia

Topics: Adult; Cannabis; Chronic Pain; Humans; Medical Marijuana; Neuralgia

Topics: Cannabis; Chronic Pain; Humans; Medical Marijuana; Neuralgia; Phytotherapy; Plant Preparations

Topics: Cannabinoids; Cannabis; Humans; Medical Marijuana; Neuralgia; Peripheral Nervous System Diseases; Phytotherapy; Plant Extracts; Sensation Disorders

Topics: Cannabis; Female; Humans; Male; Neuralgia; Phytotherapy

Topics: Cannabis; Female; Humans; Male; Neuralgia; Phytotherapy

GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also by certain cannabinoids. In this study, we investigated the GPR55 pharmacology of various cannabinoids, including analogues of the CB1 receptor antagonist Rimonabant®, CB2 receptor agonists, and Cannabis sativa constituents. To test ERK1/2 phosphorylation, a primary downstream signaling pathway that conveys LPI-induced activation of GPR55, a high throughput system, was established using the AlphaScreen® SureFire® assay. Here, we show that CB1 receptor antagonists can act both as agonists alone and as inhibitors of LPI signaling under the same assay conditions. This study clarifies the controversy surrounding the GPR55-mediated actions of SR141716A; some reports indicate the compound to be an agonist and some report antagonism. In contrast, we report that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling. GPR55 has been implicated in pain transmission, and thus our results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands. The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI. These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.

Topics: Allosteric Regulation; Analgesics; Cannabinoids; Cannabis; Dronabinol; HEK293 Cells; Humans; Ligands; Lysophospholipids; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Neuralgia; Phosphoproteins; Phosphorylation; Piperidines; Plant Extracts; Pyrazoles; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Rimonabant

Topics: Analgesics; Cannabis; Drug Therapy, Combination; Female; Humans; Ketamine; Middle Aged; Neuralgia; Pain, Intractable; Ulnar Nerve Compression Syndromes

Fourteen states and the District of Columbia have legalized the use of cannabis for medical purposes. A small, high-quality literature supports the efficacy of medical cannabis for the treatment of neuropathic pain. The smoked botanical product, however, is associated with a number of adverse medical and psychiatric consequences. Furthermore, experimental data indicate that acute use of cannabis results in impairment of every important metric related to the safe operation of a motor vehicle. Epidemiological data show associations between recent cannabis use and both psychomotor impairment and motor vehicle crashes, associations that are strengthened by the concomitant use of alcohol and other central nervous system depressants. Finally, data from pain clinics reveals an unusually high prevalence of cannabis use in nearly all age groups and an association between cannabis use and opioid and other substance misuse. Based on available data and expert opinion, concomitant use of cannabis and opioids is an absolute contraindication to the operation of a motor vehicle. In patients who use cannabis and are prescribed opioids, heightened vigilance for opioid- and other substance-related problems is warranted. It is appropriate to refrain from prescribing opioids to individuals using medical cannabis if there is reasonable suspicion that the combination will pose a risk to the patient or others.

Topics: Accidents, Traffic; Alcohol Drinking; Analgesics, Opioid; Animals; Cannabis; Drug Interactions; Humans; Marijuana Smoking; Neuralgia; Opioid-Related Disorders; Phytotherapy; Substance-Related Disorders; United States

Topics: Administration, Oral; Administration, Sublingual; Cannabinoids; Cannabis; Dronabinol; Humans; Marijuana Smoking; Meta-Analysis as Topic; Multiple Sclerosis; Neuralgia; Pain; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic

Topics: Canada; Cannabidiol; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Humans; Multiple Sclerosis; Neuralgia; Phytotherapy; Plant Extracts

Topics: Adult; Cannabis; Female; HIV Infections; Humans; Male; Neuralgia; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic

Topics: Administration, Oral; Affect; Appetite; Cannabidiol; Cannabinoids; Cannabis; Clinical Trials, Phase III as Topic; Double-Blind Method; Dronabinol; Humans; Multiple Sclerosis; Muscle Spasticity; Neuralgia; Plant Extracts; Reflex, Abnormal; Safety; Sleep; Switzerland; Treatment Outcome; United Kingdom