Opioid and healthcare service use in medical cannabis patients with chronic pain: a prospective study.

BACKGROUND: Various jurisdictions have legalised medical cannabis (MC) for use in chronic pain treatment. The objective of this study was to determine if the use of MC is related to a reduction in the use of prescription opioids and other prescription medications and healthcare services. METHODS: A retrospective cohort study was conducted using the medical files of 68 Israeli patients with chronic pain using MC. Number of prescription medications filled and healthcare services used were recorded separately for the baseline period (6 months prior to the start of MC treatment) and 6 months' follow-up. Paired t-tests were used to compare each individual to himself/herself from baseline to follow-up. RESULTS: Patients filled less opioid prescription medication at follow-up compared with baseline, and the reduction was of small effect size. There were no significant changes in the use of other medications or use of healthcare services from pre-MC treatment to follow-up. CONCLUSIONS: MC may be related to a significant yet small reduction in opioid prescription medication. Further prospective studies with representative samples are warranted to confirm the potential small opioid-sparing effects of MC treatment, its clinical importance, if any, and potential lack of association with other healthcare-related services and medication use. Due to methodological limitations of the data used in this study, results may be regarded as preliminary and causal inferences cannot be made.

The rise and fall of mandrake in medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Mandrake (Mandragora sp.) is one of the most famous medicinal plants. It has been in continuous medical use throughout written history and is still in use today in popular medicine. AIM OF THE STUDY: Mandrake derived drugs once played an important role in medicine and in magical practices. Today, the role of mandrake in popular medicine is marginal. However, natural products present in mandrake such as atropine and scopolamine, as well as their semi synthetic derivatives continue to hold and important role in medicine. Here we aim to trace the development of historical rationales and scientific events that led to the abandonment of mandrake as a medicine. MATERIALS AND METHODS: We review the medicinal uses of mandrake drugs since antiquity in an attempt to pinpoint use patterns that were popular in certain periods of time and others that are more general. We compare the uses from the native territories to those from regions where the plant got introduced and use literature reporting mandrake's chemistry and pharmacology in order to explain the diachronic changes of use patterns. RESULTS AND CONCLUSION: We found information about 88 different medicinal uses for mandrake, grouped into 39 conditions. According to the number of different medicinal uses, the most versatile period was the medieval (37), followed by the Renaissance (31), the classical (27), and the modern period (21). Considering the higher number of textual sources and use-records collected for the Renaissance period, the decrease of versatility in comparison to the medieval period appears robust. This seems to indicate a more consolidated use pattern, that might be conditioned by the reproduction of classic textual sources as well as by a less experimental approach and reduced popularity of mandrake in medicine. The introduction of the volatile anaesthetics with more reliable narcotic effects set the seal on using mandrake in surgery but opened the way for atropine being used as a prophylactic and antidote during surgical interventions.

Differential Sensitization of Muscle versus Fascia in Individuals with Low Back Pain.

Muscles and the deep fascia surrounding them have been suggested to play an important role in various musculoskeletal pain conditions including low back pain. Both have been shown to host rich nociceptive innervation and to undergo changes in individuals with chronic pain. However, evidence for the respective contribution of muscle and fascia sensitization in humans with myofascial pain syndrome is lacking. Here, we studied the sensitization of muscle and fascia in individuals with myofascial low back pain. Twenty individuals with acute (5) and chronic (15) myofascial low back pain of the quadratus lumborum muscle and a matched control group of twenty healthy individuals were recruited and clinically evaluated. All participants underwent ultrasound-guided needling of their subcutaneous tissue, deep fascia and quadratus lumborum muscle. Reported pain intensity and episodes of muscle twitching were recorded and analyzed. Among pain patients, both muscles and deep fascia demonstrated pain hypersensitivity, but muscles were significantly more sensitized than the deep fascia. No difference between acute- or chronic-pain patients was observed. Results of this study suggest that while both deep fascia and muscle show pain sensitization in both early and chronic stages of low back pain, muscles are more sensitized than fascia.

Medical Cannabis Use and Pain: An Experience Sampling Study.

Background: Little research has tested associations of pain and MC use after long-term treatment and through methods that have external validity outside experimental settings. The study examined associations of pain, associated painful experiences, and long-term medical cannabis (MC) use in chronic pain (CP) patients using a naturalistic daily diary study that provided novel and externally valid data. Methods: Data were obtained from 78 MC users with CP three times daily over a 10-day period (nobservations = 1,688). Mixed-effects models were used to test the associations between MC use and momentary experiences of pain, affect, and fatigue. Results: Within persons, elevated experiences of pain intensity were associated with greater intention to use MC within the next hour. No evidence was found that the time lapse since last MC use was associated with pain levels, negative affect, or fatigue. Conclusions: The results imply that after long-term use, CP patients intend to use MC in response to pain experiences. Yet, they may not actually achieve the pain relief. More research is needed to examine whether continued MC use despite lack of pain relief is related to relief of other symptoms (e.g., dependence, withdrawal) or positive benefits (e.g., general sense of well-being) or tolerance.

Medical cannabis and cognitive performance in middle to old adults treated for chronic pain.

INTRODUCTION AND AIMS: Cannabis exposure is becoming more common in older age but little is known about how it is associated with brain health in this population. This study assesses the relationship between long-term medical cannabis (MC) use and cognitive function in a sample of middle-aged and old chronic pain patients. DESIGN AND METHODS: A cross-sectional study was conducted among chronic pain patients aged 50+ years who had MC licenses (n = 63) and a comparison group who did not have MC licenses (n = 62). CogState computerised brief battery was used to assess cognitive performance of psychomotor reaction, attention, working memory and new learning. Regression models and Bayesian t-tests examined differences in cognitive performance in the two groups. Furthermore, the associations between MC use patterns (dosage, cannabinoid concentrations, length and frequency of use and hours since last use) with cognition were assessed among MC licensed patients. RESULTS: Mean age was 63 ± 6 and 60 ± 5 years in the non-exposed and MC patients, respectively. Groups did not significantly differ in terms of cognitive performance measures. Furthermore, none of the MC use patterns were associated with cognitive performance. DISCUSSION AND CONCLUSIONS: These results suggest that use of whole plant MC does not have a widespread impact on cognition in older chronic pain patients. Considering the increasing use of MC in older populations, this study could be a first step towards a better risk-benefit assessment of MC treatment in this population. Future studies are urgently needed to further clarify the implications of late-life cannabis use for brain health.

Medical cannabis treatment for chronic pain: Outcomes and prediction of response.

BACKGROUND: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. METHODS: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). RESULTS: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. CONCLUSIONS: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

The Case for Comorbid Myofascial Pain-A Qualitative Review.

Myofascial pain syndrome is widely considered to be among the most prevalent pain conditions, both in the community and in specialized pain clinics. While myofascial pain often arises in otherwise healthy individuals, evidence is mounting that its prevalence may be even higher in individuals with various comorbidities. Comorbid myofascial pain has been observed in a wide variety of medical conditions, including malignant tumors, osteoarthritis, neurological conditions, and mental health conditions. Here, we review the evidence of comorbid myofascial pain and discuss the diagnostic and therapeutic implications of its recognition.

The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Precise cannabis treatment dosing remains a major challenge, leading to physicians' reluctance to prescribe medical cannabis. OBJECTIVE: To test the pharmacokinetics, analgesic effect, cognitive performance and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ9 -Tetrahydrocannabinol (THC) in patients with chronic pain. METHODS: In a randomized, three-arms, double-blinded, placebo-controlled, cross-over trial, 27 patients received a single inhalation of Δ9 -THC: 0.5mg, 1mg, or a placebo. Δ9 -THC plasma levels were measured at baseline and up to 150-min post-inhalation. Pain intensity and safety parameters were recorded on a 10-cm visual analogue scale (VAS) at pre-defined time points. The cognitive performance was evaluated using the selective sub-tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: Following inhalation of 0.5 mg or 1mg, Δ9 -THC plasma Cmax  ± SD were 14.3 ± 7.7 and 33.8 ± 25.7 ng/ml. Tmax  ± SD were 3.7 ± 1.4 and 4.4 ± 2.1 min, and AUC0  â†’ infinity ±SD were 300 ± 144 and 769 ± 331 ng*min/ml, respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150-min. The 1-mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance. CONCLUSION: This feasibility trial demonstrated that a metered-dose cannabis inhaler delivered precise and low THC doses, produced a dose-dependent and safe analgesic effect in patients with neuropathic pain/ complex-regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models. SIGNIFICANCE: Evidence suggests that cannabis-based medicines are an effective treatment for chronic pain in adults. The pharmacokinetics of THC varies as a function of its route of administration. Pulmonary assimilation of inhaled THC causes rapid onset of analgesia. However, currently used routes of cannabinoids delivery provide unknown doses, making it impossible to implement a pharmaceutical standard treatment plan. A novel selective-dose cannabis inhaler delivers significantly low and precise doses of THC, thus allowing the administration of inhaled cannabis-based medicines according to high pharmaceutical standards. These low doses of THC can produce safe and effective analgesia in patients with chronic pain.

Cannabis and Pain Treatment-A Review of the Clinical Utility and a Practical Approach in Light of Uncertainty.

Over the past decade the phenomenon of cannabis as a legitimate form of treatment for pain has overwhelmed the medical community, especially in the field of pain. From a status of a schedule 1 substance having no currently accepted medical use and being considered to have high potential for abuse, its use has mushroomed to over 50,000 legal medical users per year in Israel alone. There appear to be many reasons behind this phenomenon-medical, sociological, and economical. Thus, what is cannabis? An abusive substance or a medication? Should it be incorporated into current biomedical practice, and how should it be administered? Finally, what is the evidence for the beneficial and detrimental effects of cannabis? This article reviews and discusses the current literature regarding the beneficial and the detrimental effects of medical cannabis in the treatment of pain. We further discuss the problems and challenges facing the medical community in this domain and offer a practical approach to deal with these challenges.

Medical cannabis and insomnia in older adults with chronic pain: a cross-sectional study.

OBJECTIVES: Medical cannabis (MC) is increasingly being used for treatment of chronic pain symptoms. Among patients there is also a growing preference for the use of MC to manage sleep problems. The aim of the current study was to examine the associations between use of whole plant cannabis and sleep problems among chronic pain patients. METHODS: A total of 128 individuals with chronic pain over the age of 50 years were recruited from the Rambam Institute for Pain Medicine in Haifa, Israel. Of them, 66 were MC users and 62 were non-users. Regression models tested the differences in sleep problems between the two groups. Furthermore, Pearson correlations between MC use measures (dose, length and frequency of use, number of strains used, tetrahydrocannabinol/cannabidiol levels) and sleep problems were assessed among MC users. RESULTS: After adjustment for age, sex, pain level and use of sleep and anti-depressant medications, MC use was associated with less problems with waking up at night compared with non-MC use. No group differences were found for problems with falling asleep or waking up early without managing to fall back asleep. Frequent MC use was associated with more problems waking up at night and falling asleep. CONCLUSIONS: MC use may have an overall positive effect on maintaining sleep throughout the night in chronic pain patients. At the same time, tolerance towards potential sleep-inducing properties of MC may occur with frequent use. More research based on randomised control trials and other longitudinal designs is warranted.

Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study.

OBJECTIVE: The objectives were to evaluate the, usability, feasibility of use, satisfaction, and safety of the Syqe Inhaler Exo (Syqe Inhaler), a metered dose, Pharmacokinetics-validated, cannabis inhaler device in a cohort of hospitalized patients that were using medical cannabis under license as a part of their ongoing medical treatment. METHOD: Before and after inhaling from the Syqe Inhaler, participants were asked to fill a questionnaire regarding pain reduction on a visual analog scale from 0 to 10 and, if relevant, reduction in chemotherapy-induced nausea and vomiting and/or spasticity. A patient satisfaction questionnaire and a usability questionnaire were filled in following the last use. Prescribed treatment included 4 daily doses of 500 µg tetrahydrocannabinol each delivered from 16 mg cannabis flos per inhalation plus up to an additional four SOS (distress code for more doses of cannabis) doses. RESULT: Daily cannabis dose consumed during hospitalization with the Syqe Inhaler was 51 mg (20-96) versus 1,000 mg (660-3,300) consumed prehospitalization. Patients were easily trained and continued to use Syqe Inhaler for the duration of their hospitalization (5 [3-7] days). Pain intensity 30-60 minutes following inhalations was reported to be significantly lower than preinhalation 4 [1-5] versus 7 [2-9]). Participants ranked their satisfaction with Syqe Inhaler as 6 (5-7). Three participants reported mild cough, which resolved spontaneously. SIGNIFICANCE OF RESULTS: Cannabis inhalation by combustion is not feasible for hospitalized patients. The use of Syqe Inhaler during hospitalization yielded high levels of patients and staff satisfaction with no complications.

Validation of Clinical Vignettes to Explore Medical Cannabis Practices.

BACKGROUND: The policies and practices related to medical cannabis are currently in flux. These changes have been associated with many controversies, and there is a lack of consensus within the medical community regarding medical cannabis practices. OBJECTIVES: To validate clinical vignettes that can be used to examine and improve medical cannabis practices. METHODS: Ten physicians participated in a Delphi survey of two consequent rounds in which they quantified the eligibility of medical cannabis therapy for six clinical vignettes describing both chronic pain and cancer patients. RESULTS: Higher consensus was achieved for the vignettes of cancer patients, which were additionally rated as more eligible for medical cannabis therapy. The highest level of consent (4.3 out of 5) was achieved regarding a vignette of a metastatic cancer patient. While in some cases physicians consolidated their ratings toward the group's average, in other cases they remained stable in their responses. CONCLUSIONS: While controversies related to medical cannabis are expected to remain rampant, the validated vignettes may facilitate assessment of clinical practices, which is essential for a successful implementation of medical cannabis policies. These vignettes may additionally be used in medical training for appropriate patient selection for medical cannabis authorization.

Predicting Physicians' Intentions to Recommend Medical Cannabis.

CONTEXT: Although medical cannabis (MC) policies continue to evolve around the world, the integration of MC into clinical practice remains highly debated within the medical community. OBJECTIVES: Relying on the Theory of Planned Behavior (TPB), this study aim was to identify underlying factors that influence physicians' intentions to recommend MC to patients and to examine whether there are differences in the strength of these associations across three medical specialties (family medicine, oncology, and pain medicine). METHODS: 247 physicians completed questionnaires including measures of TPB constructs (attitudes, subjective norms, and perceived behavioral control) and intentions to recommend MC to two clinical vignettes describing medical background of a cancer and a chronic pain patient. Regression models were used to measure the extent to which perceived knowledge and TPB constructs predict physicians' intentions to recommend MC. RESULTS: Physicians' intentions to recommend MC to the cancer patient vignette was higher than their intentions to recommend to the chronic pain patient vignette. Intentions to recommend MC to the patient with cancer were associated with more favorable attitudes toward MC, whereas intentions to recommend MC to the patient with chronic pain were associated with more favorable attitudes, higher levels of perceived control, and lower levels of perceived knowledge. CONCLUSION: Clinical practices related to MC may be influenced by nonmedical factors, and this may be particularly prevailing in the field of chronic pain, suggesting that MC may be particularly contentious in this field.

Rhetorical and regulatory boundary-work: The case of medical cannabis policy-making in Israel.

Recent studies have explored how professionals draw boundaries to reach workable solutions in conflictual and contested areas. Yet they neglected to explore the relationships and dynamics between how boundaries are demarcated in rhetoric and in policy. This article examines these relationships empirically through the case of medical cannabis (MC) policy-making in Israel. Drawing on interviews with key stakeholders in the MC policy field, formal policy documents, and observations of MC conferences, this article sheds light on the dynamics between rhetorical boundary-work and what we term regulatory boundary-work, namely setting rules and regulations to demarcate boundaries in actual practice. Results show how certain definitions of and rationales for a discursive separation between "medical" and "recreational" cannabis and between cannabis "medicalization" and "legalization" prevailed and were translated into formal policy, as well as how stakeholders' reactions to this boundary-work produced policy changes and the shifting of boundaries. Both rhetorical and regulatory boundary-works emerge as ongoing contested processes of negotiation, which are linked in a pattern of reciprocal influence. These processes are dominated by certain actors who have greater power to determine how and why specific boundaries should be drawn instead of others.

Challenging the Cinderella Hypothesis: A New Model for the Role of the Motor Unit Recruitment Pattern in the Pathogenesis of Myofascial Pain Syndrome in Postural Muscles.

BACKGROUND: The energy crisis hypothesis, which is a widely accepted model for the pathogenesis of myofascial pain, has been corroborated by experimental observations. However, the nature of the insult leading to the energy crisis remains elusive. A commonly cited model for this insult is the Cinderella hypothesis, suggesting that hierarchical recruitment of motor units leads to a disproportional load on small units, thus driving them towards an energy crisis. New findings cast doubt on this model, showing that in postural muscles motor units are recruited in rotation, rather than in a hierarchical order, precluding the formation of the so-called Cinderella units. OBJECTIVE: To explore the influence of common myofascial predisposing factors such as muscle load and muscle strength on the relaxation time of postural muscle motor units, assuming they are recruited in rotation. METHODS: A stochastic model of a postural skeletal muscle was developed which integrates the energy crisis model and motor unit rotation patterns observed in postural muscles. Postulating that adequate relaxation time is essential for the energetic replenishment of motor units, we explored the influence of different parameters on the relaxation time of individual motor units under varying conditions of muscle loads and muscle strengths. RESULTS: The motor unit relaxation/contraction time ratio decreases with elevated muscle loads and with decreased total muscle strength. CONCLUSIONS: In a model of a postural muscle, in which motor units are recruited in rotation, common predisposing factors of myofascial pain, such as increased muscle load and decreased muscle force, lead to shortened motor unit relaxation periods.

Twenty Thousand Needles Under the Sea. Trigger Point Dry Needling Aboard an Israeli Navy Submarine: A Case Report.

Nonspecific lower back pain affects a major part of the population at a certain point of their life. The intensity of pain can be debilitating and it causes a significant burden on society. Trigger point dry needling is a method of alleviating such pain by the introduction of needles into trigger points in muscles. A growing body of evidence supports its use in myofascial pain and specifically lower back pain. Submarine Medicine is a unique field due to the special characteristics and the environment of the submarine. It poses challenges that are not always seen by primary care physicians. Here, we present a case of a 40-yr-old senior submarine officer who complained of pain in his lower back and pelvis before departing on a mission. The pain persisted in spite of treatment with nonsteroidal anti-inflammatory drugs and he was then treated by the submarine's physician with trigger point dry needling. The officer showed rapid improvement following this treatment, both regarding pain and the range of motion.

Medical cannabis: An oxymoron? Physicians' perceptions of medical cannabis.

BACKGROUND: Medical cannabis policies are changing in many places around the world, and physicians play a major role in the implementation of these policies. The aim of this study was to gain a deeper understanding of physicians' views on medical cannabis and its possible integration into their clinic, as well as to identify potential underlying factors that influence these perceptions. METHODS: Qualitative narrative analysis of in-depth interviews with twenty-four Israeli physicians from three specialties (pain medicine, oncology and family medicine). FINDINGS: Physicians disclosed contrasting narratives of cannabis, presenting it as both a medicine and a non-medicine. These divergent positions co-existed and were intertwined in physicians' accounts. When presenting cannabis as a non-medicine, physicians drew on conventional medicine and prohibition as narrative environments. They emphasized the incongruence of cannabis with standards of biomedicine and presented cannabis as an addictive drug of abuse. In contrast, physicians drew upon unconventional medicine and palliative care as narrative environments while presenting cannabis as a medicine. In this narrative, physicians emphasized positive hands-on experiences with cannabis, and pointed to the limits of conventional medicine. CONCLUSION: Physicians did not have a consolidated perspective as to whether cannabis is a medicine or not, but rather struggled with this question. The dualistic narratives of cannabis reflect the lack of a dominant narrative environment that supports the integration of cannabis into medical practice. This may in turn indicate barriers to the implementation of medical cannabis policies. An awareness of physicians' views and the different levels of their willingness to implement medical cannabis policies is essential for policy developments in this evolving field.

Medical students' attitudes towards participating in a palliative medicine course: A new specialty in Israel.

BACKGROUND: Palliative medicine is a growing field in Israel, and its training program is still in process. The current study aimed to evaluate students' attitudes regarding a course in palliative care established in a division of oncology. METHOD: Some 45 medical students in their 5th to 6th years participated in a one-week course on palliative care. At the end of each training week, students were asked to complete a questionnaire, evaluating their attitudes regarding different aspects of the program content, such as its importance and relevance to their training as physicians, as well as the contribution of specific parts of the program to their knowledge regarding palliative care. RESULTS: The overall satisfaction of the 45 students was high. The most contributory parts of the course were the multidisciplinary team and the complementary and alternative medicine. Participating in the staff meetings and accompanying physicians in their daily work were scored as the least contributory parts.Significance of resultsThis preliminary study demonstrated students' overall high satisfaction with the newly established palliative care course and their need for more practical skills. Future studies should investigate and evaluate educational programs in palliative care in order to establish suitable training for medical students.