Fetal Cannabinoid Syndrome: Behavioral and Brain Alterations of the Offspring Exposed to Dronabinol during Gestation and Lactation.

This study establishes a fetal cannabinoid syndrome model to evaluate the effects of high doses of dronabinol (synthetic THC) during pregnancy and lactation on behavioral and brain changes in male and female progeny and their susceptibility to alcohol consumption. Female C57BL/6J mice received dronabinol (10 mg/kg/12 h, p.o.) from gestational day 5 to postnatal day 21. On the weaning day, the offspring were separated by sex, and on postnatal day 60, behavioral and neurobiological changes were analyzed. Mice exposed to dronabinol exhibited increased anxiogenic and depressive-like behaviors and cognitive impairment. These behaviors were associated with neurodevelopment-related gene and protein expression changes, establishing, for the first time, an association among behavioral changes, cognitive impairment, and neurobiological alterations. Exposure to dronabinol during pregnancy and lactation disrupted the reward system, leading to increased motivation to consume alcohol in the offspring. All these modifications exhibited sex-dependent patterns. These findings reveal the pronounced adverse effects on fetal neurodevelopment resulting from cannabis use during pregnancy and lactation and strongly suggest the need to prevent mothers who use cannabis in this period from the severe and permanent side effects on behavior and brain development that may occur in their children.

Treating nightmares in posttraumatic stress disorder with dronabinol: study protocol of a multicenter randomized controlled study (THC PTSD-trial).

BACKGROUND: Distressing nightmares are a core symptom of posttraumatic stress disorder (PTSD) and contribute to psychiatric comorbidity, impaired physical health and decreased social functioning. No specific pharmacological treatment for PTSD-related nightmares is yet approved. Preliminary clinical data indicate that cannabinoid agonists can improve nightmares and overall PTSD symptoms in patients with PTSD. The primary objective of the study is to examine the efficacy of oral dronabinol (BX-1) versus placebo in reducing nightmares in patients with PTSD. The secondary objectives of the study are to examine the efficacy of oral BX-1 in reducing other PTSD symptoms. METHODS: The study is designed as a multi-centric, double-blind, randomized (1:1), placebo-controlled, parallel group interventional trial. Eligible patients will be randomized to BX-1 or placebo, receiving a once-daily oral dose before bedtime for 10 weeks. Primary efficacy endpoint is the Clinician-Administered PTSD Scale (CAPS-IV) B2 score for the last week, measuring frequency and intensity of nightmares. Secondary efficacy endpoints are other disorder-specific symptoms in patients with PTSD. Further, tolerability and safety of dronabinol will be assessed. DISCUSSION: This randomized controlled trial will provide evidence whether treating patients with PTSD and nightmares with dronabinol is safe and efficacious. TRIAL REGISTRATION: NCT04448808, EudraCT 2019-002211-25.

[Use of dronabinol in the treatment of resistant neuropathic pain: Feedback from patients followed in a multidisciplinary pain center]. / Utilisation du dronabinol dans le traitement des douleurs neuropathiques réfractaires : retour d'expérience des patients suivis dans un Centre d'évaluation et de traitement de la douleur.

INTRODUCTION: Dronabinol is a drug composed of synthetic delta-9-tetrahydrocannabinol. In France, dronabinol requires a named Temporary Utilisation Authorisation (TUA), for the treatment of refractory neuropathic pain. Few data currently exist concerning its efficacy and tolerance. We present our feedback on its use for chronic pain patients, the multidisciplinary supervision and the monitoring set up by the clinical pharmacist. METHOD: This retrospective monocentric study presents Patients Global Impression of Change and tolerance data from patients treated with dronabinol in a pain center between October 2020 and July 2021. We present their satisfaction towards the care process. RESULTS: Nineteen patients were treated with dronabinol during the study period. - The clinical pharmacist issued 180 advices for patients and doctors. Patients reported a positive impact of the telephone follow-up carried out by the clinical pharmacist. - 75% (n=9/12) of patients who continued treatment for more than 3 months reported improvement in their health. - 74% (n=14/19) of patients had at least one adverse event, six patients needed to discontinue the treatment. DISCUSSION-CONCLUSION: Dronabinol represents an alternative that can improve the quality of life of some patients suffering from refractory neuropathic pain. Nevertheless, as with any medicine, its initiation requires a rigorous evaluation of the benefit-risk balance. The close collaboration between the physician and the clinical pharmacist allows a secure management patients and makes this complex drug circuit easer.

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry.

OBJECTIVE: To evaluate the effectiveness of Δ9-tetrahydrocannabinol (dronabinol [DRO]) as an add-on treatment in patients with refractory chronic pain (CP). METHODS: An exploratory retrospective analysis of 12-week data provided by the German Pain e-Registry on adult patients with treatment refractory CP who received DRO. RESULTS: Between March 10, 2017, and June 30, 2019, the German Pain e-Registry collected information on 89,095 patients with pain, of whom 1,145 patients (1.3%) received DRO (53.8% female, mean ± standard deviation age: 56.9 ± 10.6 years), and 70.0% documented use for the entire 12-week evaluation period. The average DRO daily dose was 15.8 ± 7.5 mg, typically in three divided doses (average DRO dose of 5.3 ± 2.1 mg). Average 24-hour pain intensity decreased from 46.3 ± 16.1 to 26.8 ± 18.7 mm on a visual analog scale (absolute visual analog scale difference: -19.5 ± 17.3; P < 0.001). Among patients who completed follow-up, an improvement from baseline of at least 50% was documented for pain (46.5%), activities of daily living (39%), quality of life (31.4%), and sleep (35.3%). A total of 536 patients (46.8%) reported at least one of 1,617 drug-related adverse events, none of which were serious, and 248 patients (21.7%) stopped treatment. Over the 12-week period, 59.0% of patients reported a reduction of other pain treatments, and 7.8% reported a complete cessation of any other pharmacological pain treatments. CONCLUSION: Add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.

The Effectiveness of Cannabis and Cannabis Derivatives in Treating Lower Back Pain in the Aged Population: A Systematic Review.

BACKGROUND/AIMS: Cannabis is increasingly used in the management of pain, though minimal research exists to support its use since approval. Reduction in stigma has led to a growing interest in pharmaceutical cannabinoids as a possible treatment for lower back pain (LBP). The objective of this review was to assess the role and efficacy of cannabis and its derivatives in the management of LBP and compile global data related to the role of cannabis in the management of LBP in an aging population. METHODS: A systematic review was conducted using predetermined keywords by 3 independent researchers. Predetermined inclusion and exclusion criteria were applied, and 23 articles were selected for further analysis. RESULTS: Studies identified both significant and insignificant impacts of cannabis on LBP. Contradicting evidence was noted on the role of cannabis in the management of anxiety and insomnia, 2 common comorbidities with LBP. The existing literature suggests that cannabis may be used in the management of LBP and comorbid symptoms. CONCLUSIONS: Further research is needed to consider cannabis as an independent management option. There is a lack of evidence pertaining to the benefits of cannabis in an aged population, and thus, additional research is warranted to support its use in the aged population.

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome.

INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients. MATERIAL AND METHODS: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: ('Tourette syndrome' [MeSH Terms] OR 'Gilles de la Tourette syndrome' [MeSH Terms] OR 'tic disorders' [MeSH Terms] OR 'tics' [MeSH Terms] OR 'tic disorders'[Title/Abstract]) AND ('cannabis-based medicine' [Title/Abstract] OR 'cannabis' [Title/Abstract] OR 'dronabinol' [Title/Abstract] OR 'nabiximols' [Title/Abstract] OR 'tetrahydrocannabinol' [Title/Abstract] OR 'THC' [Title/Abstract] OR 'cannabidiol' [Title/Abstract], limit: 'humans'. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV). RESULTS: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant. CONCLUSIONS: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS.

THC shows activity against cultured Plasmodium falciparum.

The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits ß-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited ß-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.

Use of Cannabis and Cannabinoids in Patients With Cancer.

OBJECTIVE: To review pharmacology, available dosage forms, efficacy, and safety of cannabis and cannabinoids in cancer patients. DATA SOURCES: In PubMed (1965 to June 2020) the search was conducted using the search terms cannabidiol, cannabis, CBD, dronabinol, endocannabinoids, medical marijuana, nabiximols, nabilone, THC, and cancer. Abstracts from article bibliographies were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies conducted in humans evaluating cannabis and cannabinoids for cancer treatment or related symptoms were considered. Reference lists in relevant articles, package inserts, guidance documents, and addditional articles evaluating cannabis and cannabinoids were identified. DATA SYNTHESIS: Cannabis and cannabinoid effectiveness can be attributed to active components delta-9-tetrahydrocannabinol and cannabidiol. Multiple dosage forms exist, each with different properties contributing to efficacy and safety differences. No data supports use as anticancer agents, and mixed efficacy results have been reported when used in cancer patients with nausea, pain, and anorexia. Inclusion of medicinal and synthetic products, small sample sizes, varying patient populations, and different dosage forms, doses, and drug combinations. These products are well tolerated, and adverse effects depend on the main active component. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Healthcare professionals need to identify appropriateness, monitor, and document use of cannabis and cannabinoids similar to other drug therapies as well as educate the patients/ caregivers about potential benefits and risks. CONCLUSIONS: Current evidence for use of medical cannabis and cannabinoids in cancer patients is weak. However, healthcare professionals are in an ideal role to monitor and educate patients using medical cannabis and cannabinoids.

Role of marijuana components on the regenerative ability of stem cells.

Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 µM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs. CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01). CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies. SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.

Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. OBJECTIVE: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN. METHOD: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines. RESULTS: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. DISCUSSION AND CONCLUSION: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology. LEVEL OF EVIDENCE: Level I, systematic review.

Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature.

OBJECTIVE: To compile and synthesize the available literature describing medical cannabis use across various disease states. DATA SOURCES: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. DATA SYNTHESIS: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. CONCLUSIONS: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.

Oral cannabinoid for the prophylaxis of chemotherapy-induced nausea and vomiting-a systematic review and meta-analysis.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a burdensome adverse event frequently associated with chemotherapy treatment of cancer. Evidence suggests that cannabinoid CB2 receptors are present in brainstem neurons, and thus, there may exist a role for cannabinoids to counter CINV. The aim of this paper is to conduct a systematic review and meta-analysis of the efficacy and safety of oral cannabinoids compared with other treatments as documented in randomized controlled trials (RCTs). METHODS: A literature search was conducted using Ovid MEDLINE up until December 31, 2018; Embase Classic and Embase up until 2018 week 53; and Cochrane Central Register of Controlled Trials up until November 2018. Study data were extracted and included in this meta-analysis if they reported on at least one of the following efficacy endpoints: no nausea and no vomiting, no nausea, and no vomiting. The Mantel-Haenszel method and random effects analysis model were used, to generate odds ratio (OR) and accompanying 95% confidence intervals (CI). RESULTS: In the setting of prophylactic treatment against both nausea and vomiting, oral cannabinoid was more efficacious than placebo or other studied antiemetic treatments. When controlling for vomiting, oral cannabinoid was equally as efficacious as others. Against nausea, oral cannabinoid was equally as effective as other treatments. A greater percentage of patients administered oral cannabinoid for CINV experienced dysphoria, euphoria, and sedation. CONCLUSION: Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date. However, there exists only a limited number of RCTs, comparisons with older treatment regimens and a lack of standard reporting practice across published literature. Further RCTs should investigate the efficacy and safety of oral cannabinoids, to secure a better picture of the efficacy of oral cannabinoids against CINV.

Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit.

BACKGROUND: Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects. AIMS: The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients' perceived benefit on their symptoms of Gp. METHODS: Patients with symptoms of Gp underwent history and physical examination, gastric emptying scintigraphy, and questionnaires assessing symptoms. Patients were asked about the current use of medications and alternative medications including marijuana. RESULTS: Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better. CONCLUSIONS: A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01696747.

Industrial, CBD, and Wild Hemp: How Different Are Their Essential Oil Profile and Antimicrobial Activity?

Hemp (Cannabis sativa L.) is currently one of the most controversial and promising crops. This study compared nine wild hemp (C. sativa spp. spontanea V.) accessions with 13 registered cultivars, eight breeding lines, and one cannabidiol (CBD) hemp strain belonging to C. sativa L. The first three groups had similar main essential oil (EO) constituents, but in different concentrations; the CBD hemp had a different EO profile. The concentration of the four major constituents in the industrial hemp lines and wild hemp accessions varied as follows: ß-caryophyllene 11-22% and 15.4-29.6%; α-humulene 4.4-7.6% and 5.3-11.9%; caryophyllene oxide 8.6-13.7% and 0.2-31.2%; and humulene epoxide 2, 2.3-5.6% and 1.2-9.5%, respectively. The concentration of CBD in the EO of wild hemp varied from 6.9 to 52.4% of the total oil while CBD in the EO of the registered cultivars varied from 7.1 to 25%; CBD in the EO of the breeding lines and in the CBD strain varied from 6.4 to 25% and 7.4 to 8.8%, respectively. The concentrations of δ9-tetrahydrocannabinol (THC) in the EO of the three groups of hemp were significantly different, with the highest concentration being 3.5%. The EO of wild hemp had greater antimicrobial activity compared with the EO of registered cultivars. This is the first report to show that significant amounts of CBD could be accumulated in the EO of wild and registered cultivars of hemp following hydro-distillation. The amount of CBD in the EO can be greater than that in the EO of the USA strain used for commercial production of CBD. Furthermore, this is among the first reports that show greater antimicrobial activity of the EO of wild hemp vs. the EO of registered cultivars. The results suggest that wild hemp may offer an excellent opportunity for future breeding and the selection of cultivars with a desirable composition of the EO and possibly CBD-rich EO production.

Grinding and Fractionation during Distillation Alter Hemp Essential Oil Profile and Its Antimicrobial Activity.

The hypothesis of this study was that we can modify the essential oil (EO) profile of hemp (Cannabis sativa L.) and obtain fractions with differential composition and antimicrobial activity. Therefore, the objective was to evaluate the effects of grinding of hemp biomass before EO extraction and fractionation during distillation on EO profile and antimicrobial activity. The study generated a several EO fractions with a diversity of chemical profile and antimicrobial activity. The highest concentrations of ß-pinene and myrcene in the EO can be obtained in the 5-10 min distillation time (DT) of ground material or in the 80-120 min DT of nonground material. High δ-3-carene and limonene EO can be obtained from 0-5 min DT fraction of nonground material. High eucalyptol EO can be sampled either in the 0-5 min DT of the ground material or in the 80-120 min of nonground material. Overall, the highest concentrations of ß-caryophyllene, α-(E)-bergamotene, (Z)-ß-farnesene, α-humulene, caryophyllenyl alcohol, germacrene D-4-ol, spathulenol, caryophyllene oxide, humulene epoxide 2, ß-bisabolol, α-bisabolol, sesquiterpenes, and cannabidiol (CBD) can be obtained when EO is sampled in the 80-120 min DT and the material is nonground. Monoterpenes in the hemp EO can be increased twofold to 85% by grinding the material prior to distillation and collecting the EO in the first 10 min. However, grinding resulted in a slight but significant decrease in the CBD concentration of the EO. CBD-rich oil can be produced by collecting at 120-180 min DT. Different EO fractions had differential antimicrobial activity. The highest antimicrobial activity of EO fraction was found against Staphylococcus aureus subsp. aureus. THC-free EO can be obtained if the EO distillation is limited to 120 min. The results can be utilized by the hemp processing industry and by companies developing new hemp EO-infused products, including perfumery, cosmetics, dietary supplements, food, and pharmaceutical industries.

Delta-9-tetrahydrocannabinol intoxication is associated with increased prefrontal activation as assessed with functional near-infrared spectroscopy: A report of a potential biomarker of intoxication.

The primary psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), binds to cannabinoid receptors (CB1) present in high concentrations in the prefrontal cortex (PFC). It is unknown whether the PFC hemodynamic response changes with THC intoxication. We conducted the first double-blind, placebo-controlled, cross-over study of the effect of THC intoxication on functional near infrared spectroscopy (fNIRS) measures of PFC activation. Fifty-four adult, regular (at least weekly) cannabis users received a single oral dose of synthetic THC (dronabinol; 5-50 mg, dose individually tailored to produce intoxication) and identical placebo on two visits at least one week apart. fNIRS recordings were obtained during a working memory task (N-Back) at three timepoints: before THC/placebo, at 100 min (when peak effects were expected), and at 200 min after THC/placebo administration. Functional data were collected using a continuous-wave NIRS device, with 8 sources and 7 detectors arrayed over the forehead, resulting in 20 channels covering PFC regions. Participants also completed frequent heart rate measures and subjective ratings of intoxication. Approximately half of participants reported significant intoxication. Intoxication ratings were not correlated with dose of THC. Increases in heart rate significantly correlated with intoxication ratings after THC dosing. Results indicated that 100 min after THC administration, oxygenated hemoglobin (HbO) response significantly increased from pre-dose HbO levels throughout the PFC in participants who reported significant intoxication. Changes in HbO response significantly correlated with self-reported intoxication at 100 min after THC administration. Among those who reported intoxication, HbO response decreased at 200 min after THC, when intoxication had largely resolved, compared to the peak THC time point. This study demonstrates that THC intoxication causes increased PFC activity, and fNIRS of the PFC can measure this effect. Increased neural activation in PFC represents a potential biomarker for cannabis intoxication.

[The use of cannabis-based drugs in pain and palliative medicine : Joint online questionnaire conducted by the Professional Association of Physicians and Psychotherapists in Pain and Palliative Medicine in Germany (BVSD), the German Pain Society, and the German Society for Pain Medicine (DGS)]. / Einsatz von Cannabisarzneimitteln in der Schmerz- und Palliativmedizin : Gemeinsame Online-Umfrage des Berufsverbands der Ärzte und Psychotherapeuten in der Schmerz- und Palliativmedizin in Deutschland e. V. (BVSD), der Deutschen Schmerzgesellschaft e. V. und der Deutschen Gesellschaft für Schmerzmedizin e. V. (DGS).

BACKGROUND AND METHODS: An online questionnaire about cannabis medication (CAM) was sent to German pain therapists 1 year after the introduction of the new act "Amendment to drug and other regulations" of 06.03.2017. RESULTS: A total of 120 pain therapists participated. Information on 1560 treated patients was analyzed. Only in the case of Dronabinol and Sativex® did at least 50% of physicians feel well informed. Requests for the coverage of costs were sent to the statuary health insurance companies for 1521 patients. These requests had already been decided for 1265 patients (83%) at the time of the questionnaire. A total of 457 requests (36.1%) were denied, including 28 requests from palliative care patients. Most of the pain therapists (67.5%) were well informed about Dronabinol, but less so about the other CAM. CONCLUSION: The study shows an information deficit in knowledge and handling of selected CAM among physicians. Given the high rejection rate, there may also be a knowledge gap on the side of the health insurances. From a certain number of patients upwards, the non-interventional accompanying survey required by law was deemed to be barely practicable from both a time and an economical point of view.

[Cannabis medicines in pain management : Interim analysis of the survey accompanying the prescription of cannabis-based medicines in Germany with regard to pain as primarily treated symptom]. / Cannabisarzneimittel in der Schmerztherapie : Zwischenauswertung der Cannabisbegleiterhebung hinsichtlich der primär behandelten Symptomatik Schmerz.

BACKGROUND: In Germany, physicians who prescribe cannabis-based medicines at the expense of the statutory health insurance are obliged to take part in an accompanying survey. Pain was the most commonly reported diagnosis, making an interim evaluation for the indication of pain feasible. METHODS: Patient-related data was transmitted to the German Federal Institute for Drugs and Medical Devices via an online portal. In addition to demographic data, information on the treated disease or symptoms, the course of therapy, adverse reactions and treatment success were evaluated. RESULTS: A total of 3138 data sets were evaluated for the main diagnosis of pain. Dronabinol was the most frequently (64%) prescribed cannabis-based drug. On average, patients were 57 years old and women and men were equally represented. Patients treated with cannabis flowers were significantly younger (48 years). The proportion of men in this group was 68% and 83% in the group of 18- to 40-year-olds. According to the assessment by treating physicians, pain was significantly improved in 35.5% of the patients. The most frequent side effects (fatigue, dizziness, nausea) corresponded to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. Treatment was discontinued in 1179 patients within 1 year. CONCLUSION: Physicians should comply with their legal obligation to participate in the accompanying survey. Pain is by far the most common diagnosis in cannabis drugs. For about one third of these patients, physicians reported a clear improvement in pain. Due to the amount of data hitherto and the limitations in the accompanying survey, the results should not be overinterpreted in terms of efficacy and should always be related to existing reviews. The lower age and higher proportion of men among patients treated with cannabis flowers were remarkable. At 37.6%, the overall drop-out rate was high. The most frequent side effects related to vigilance and are therefore highly relevant in terms of driving ability, work ability and risk of falling. For a differentiated evaluation of treatment success, more data needs to be available.

[High-dose dronabinol treatment vs. medicinal cannabis flowers]. / Hochdosisdronabinoltherapie vs. Medizinalcannabisblüten.

This article reports a case of pronounced, chronic lumboischialgia, which was not satisfactorily controlled by conventional analgesic treatment. The level of pain under high-dose dronabinol treatment with oral and inhalative administration as well as the way to reimburse the cost of medicinal cannabis flowers, the treatment success and criteria of the economic prescription procedure are presented.