Standardized Cannabis Research Articles

Effects of standardized Cannabis sativa extract and ionizing radiation in melanoma cells in vitro.

Melanoma causes the highest number of skin cancer-related deaths worldwide. New treatment methods are essential for the management of this life-threatening disease. In this study, we investigated the efficacy of a standardized Cannabis sativa extract alone or in combination with single radiation dose (6 Gy) in B16F10 mouse melanoma cells in an extract dose-dependent manner. C. sativa extract at three concentrations (25, 12.5, and 6.25 μg/mL) alone for 72 h or in combination with radiation (24 h incubation after the extract treatment + 48 h incubation after exposure to radiation) were evaluated for cell viability of melanoma cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cells were also treated with 6.25 μg/mL extract alone for 72 h before analyzing C. sativa-induced cell death by flow cytometry. Administration of the extract alone or alongside radiation substantially inhibited melanoma cell viability and proliferation in the extract dose response-dependent manner. The inhibition of melanoma cell viability was paralleled by an increase in necrosis but not apoptosis when melanoma cells were treated with the extract alone. Radiation alone did not have any antiproliferative effects, and radiation also did not synergize antiproliferative effects of the extract when the extract and radiation were combined. Our data suggest that C. sativa extract may have significant health and physiological implications for the treatment of melanoma. The results of this study also indicate that B16F10 mouse melanoma cells are radioresistant. Taken together, these findings may lead to the identification of new therapeutic strategy for the management of melanoma.

Supercritical carbon dioxide Cannabis sativa L. and Humulus lupulus extracts and their influence on human macrophages inflammatory state*

Herbal extracts are promising immunomodulating compounds. Their standardization may improve clinical outcome in various conditions related to inflammatory state. The aim of this study was to assess the utility of Cannabis sativa L. and Humulus lupulus extracts obtained by supercritical carbon dioxide (scCO2) in the reduction of pro-inflammatory cytokines release after LPS stimulation in the in vitro model. After scCO2 extraction, the cytotoxic potential of the obtained compounds was determined. The highest non-cytotoxic concentrations were selected for further inflammatory testing. PMA-differentiated U937 cells were used as an LPS induced model of the inflammation to assess the extracts potential to decrease the level of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. Either individually tested or in combination scCO2 extracts markedly reduced the level of released pro-inflammatory cytokines in comparison to LPS stimulated positive control. Our results show that the usage of standardized Cannabis sativa L. and Humulus lupulus extracts might be beneficial in reducing the inflammatory state. Application of the mixed extracts not only reduces the need for a high concentration of pure compounds, but also broadens the possible therapeutic effect. Moreover, scCO2 extraction may serve as the efficient method of obtaining functional anti-inflammatory extracts from either hop cones or cannabis.

Cannabis and glaucoma: A literature review

Introduction: Primary open-angle glaucoma (POAG) is characterized by the loss of retinal ganglion cells secondary to optic neuropathy; increased intraocular pressure (IOP) may or may not be present. Many treatment options focus on decreasing IOP measurements to attempt to prevent progression of glaucoma. Our literature review addressed a relatively common question; if cannabis is effective for treating elevated IOP in patients with glaucoma. Objective: To evaluate the current evidence for the use of cannabis for reducing IOP in glaucoma. Methods: PubMed, Embase, and the Cochrane Database were searched along with references drawn from full text articles published before January 2018 for the best available evidence that met the inclusion criteria.Three authors independently evaluated and selected the articles that represented the best available evidence.The selected articles were chosen based on study methodology and the type of cannabis used for the treatment of glaucoma. Randomized Control Trials were preferred, although lacking. No studies directly compared cannabis to the current standard of care medications for lowering IOP. Results: Five randomized controlled trials were included as best available evidence although they used different routes of administration. All studies included compared cannabis to placebo. The studies evaluated showed a range of IOP lowering effects and side effects.Topical administration has shown conflicting results for the treatment of glaucoma.Conclusion:The many forms of cannabinoid administration have demonstrated variable levels of effectiveness. The variability of the studies indicates the need for more research. Specifically, larger sample sizes, and comparison of standardized cannabis to current standards of care instead of placebo are strongly encouraged.

'Standard THC units': a proposal to standardize dose across all cannabis products and methods of administration.

Cannabis products are becoming increasingly diverse, and vary considerably in concentrations of ∆9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Higher doses of THC can increase the risk of harm from cannabis, while CBD may partially offset some of these effects. Lower Risk Cannabis Use Guidelines currently lack recommendations based on quantity of use, and could be improved by implementing standard units. However, there is currently no consensus on how units should be measured or standardized among different cannabis products or methods of administration. Existing proposals for standard cannabis units have been based on specific methods of administration (e.g. joints) and these may not capture other methods, including pipes, bongs, blunts, dabbing, vaporizers, vape pens, edibles and liquids. Other proposals (e.g. grams of cannabis) cannot account for heterogeneity in THC concentrations among different cannabis products. Similar to alcohol units, we argue that standard cannabis units should reflect the quantity of primary active pharmacological constituents (dose of THC). On the basis of experimental and ecological data, public health considerations and existing policy, we propose that a 'standard THC unit' should be fixed at 5mg THC for all cannabis products and methods of administration. If supported by sufficient evidence in future, consumption of standard CBD units might offer an additional strategy for harm reduction. Standard ∆9 -tetrahydrocannabinol (THC) units can potentially be applied among all cannabis products and methods of administration to guide consumers and promote safer patterns of use.

The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis

ObjectivesTo determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events. Data sourcesA systematic search was performed in PubMed, ScienceDirect, ClincalTrials.gov, Scopus, Cochrane Library, and Embase from inception until June 2017. Study selectionRandomized controlled trials investigating the effects of cannabis or cannabinoids on pain reduction. Data extractionTwo reviewers extracted and assessed the quality of studies by means of Cochrane risk of bias. Standardized mean difference (SMD) was calculated. Random-effects model was undertaken to pool the treatment effects. ResultsA total of 25 studies involving 2270 patients were included. We found that delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) (oromucosal route), THC (oromucosal route), and standardized dried cannabis (with THC; SCT; inhalation route) could reduce neuropathic pain score (SMD −0.41, 95% CI −0.7 to −0.1; −0.61, 95% CI −1.2 to −0.02; and −0.77, 95% CI −1.4 to −0.2; respectively). For nociceptive pain, only standardized cannabis extract (with THC; SCET) via oral route could reduce pain score (SMD −1.8, 95% C; −2.4 to −1.2). In cancer pain, THC/CBD via oromucosal route and THC via oral or oromucosal route could reduce pain score (SMD −0.7, 95% CI −1.2 to −0.2; and −2.1, 95% CI −2.8 to −1.4; respectively). No study was observed for THC/CBD via oral route or inhalation or THC via inhalation for cancer and nociceptive pain, SCET via oromucosal route or inhalation for neuropathic and cancer pain, THC via oromucosal route for nociceptive pain, and SCT via oromucosal or oral route for neuropathic, cancer, and nociceptive pain. Statistically significant increased risks of euphoria were observed in THC/CBD (oromucosal), THC (oromucosal), and SCT (inhalation). ConclusionThe use of cannabis and cannabinoids via certain administration routes could reduce different types of pain. Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved.

Comparison of different methods for the extraction of cannabinoids from cannabis

Cannabis oils, namely concentrated cannabis extracts, are getting plenty of attention because of their therapeutic potential for treatment of patients with cancer, HIV, multiple sclerosis and several other pathologies. Here we propose the use of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) as alternative methods to the current protocols followed by pharmacists, the only authorized to manipulate standardized Cannabis. A third method, consisting of the use of Tween 20 as surfactant, was considered. Our best extraction methodology for commercial hemp extraction was applied to medicinal cannabis. Here we report the results obtained for ‘Eletta campana’, ‘Carmagnola selezionata’, Bediol®, FM2® and Bedrocan®.

Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer

Breast cancer is the second leading cause of death among women. Although early diagnosis and development of new treatments have improved their prognosis, many patients present innate or acquired resistance to current therapies. New therapeutic approaches are therefore warranted for the management of this disease. Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer. Most of these studies have been conducted with pure compounds, mainly Δ9-tetrahydrocannabinol (THC). The cannabis plant, however, produces hundreds of other compounds with their own therapeutic potential and the capability to induce synergic responses when combined, the so-called “entourage effect”. Here, we compared the antitumor efficacy of pure THC with that of a botanical drug preparation (BDP). The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+ and triple-negative breast cancer. This increased potency was not due to the presence of the 5 most abundant terpenes in the preparation. While pure THC acted by activating cannabinoid CB2 receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. The combination of cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and lapatinib, respectively) or with cisplatin, produced additive antiproliferative responses in cell cultures. Combinations of these treatments in vivo showed no interactions, either positive or negative. Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer.

Psychoactive constituents of cannabis and their clinical implications: a systematic review.

Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to cannabis psychoactivity, considering their reported concentrations and pharmacodynamics in humans. Design Following PRISMA guidelines, papers published before March 2016 in Medline, Scopus-Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a-priori selection criteria have been included. Results In 40 original papers, three naturally present cannabinoids (∆-9-Tetrahydrocannabinol, ∆-8-Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had clinical relevance. Of these, the metabolite produces the greatest psychoactive effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on cannabis psychoactive effects. The proportion of 9-THC in plant material is higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports vary due to differences in methodological aspects (doses, administration route and volunteers' previous experience with cannabis). Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity. Due to lower psychoactive potency and smaller proportions in plant material, other psychoactive cannabinoids have a weak influence on cannabis final effects. Current lack of standard methodology hinders homogenized research on cannabis health effects. Working on a standard cannabis unit considering 9-THC is recommended.

The Effects of Social Presence on Adherence-Focused Guidance in Problematic Cannabis Users: Protocol for the CANreduce 2.0 Randomized Controlled Trial.

BackgroundIn European countries, including Switzerland, cannabis is the most commonly used illicit drug. Offering a Web-based self-help tool could potentially reach users who otherwise would not seek traditional help. However, such Web-based self-help tools often suffer from low adherence.ObjectiveThrough adherence-focused guidance enhancements, the aim of this study was to increase adherence in cannabis users entering a Web-based self-help tool to reduce their cannabis use and, in this way, augment its effectiveness.MethodsThis paper presents the protocol for a three-arm randomized controlled trial (RCT) to compare the effectiveness of (1) an adherence-focused, guidance-enhanced, Web-based self-help intervention with social presence; (2) an adherence-focused, guidance-enhanced, Web-based self-help intervention without social presence; and (3) a treatment-as-usual at reducing cannabis use in problematic users. The two active interventions, each spanning 6 weeks, consist of modules designed to reduce cannabis use and attenuate common mental disorder (CMD) symptoms, including depression, anxiety, and stress-related disorder symptoms based on the approaches of motivational interviewing and cognitive behavioral therapy. With a target sample size of 528, data will be collected at baseline, 6 weeks, and 3 months after baseline. The primary outcome measurement will be the number of days of cannabis use on the preceding 7 days. Secondary outcomes will include the quantity of cannabis used in standardized cannabis joints, the severity of cannabis dependence, changes in CMD symptoms, and adherence to the program. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models.ResultsThe project commenced in August 2016; recruitment is anticipated to end by December 2018. First results are expected to be submitted for publication in summer 2019.ConclusionsThis study will provide detailed insights on if and how the effectiveness of a Web-based self-help intervention aiming to reduce cannabis use in frequent cannabis users can be improved by theory-driven, adherence-focused guidance enhancement.Trial RegistrationInternational Standard Randomized Controlled Trial Number Registry: ISRCTN11086185; http://www.isrctn.com/ISRCTN11086185 (Archived by WebCite at http://www.webcitation.org/6wspbuQ1M)

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

Objective(s):Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line.Materials and Methods:In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis.Results:Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls.Conclusion:C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

The manufacture of filtered cannabis cigarettes: uniform particle distribution and combustion properties for consistent cannabinoid delivery

Here we describe a manufacturing process for the production of commercial filtered Cranfords cannabis cigarettes (CN). Unlike production of filtered tobacco cigarettes, standardization in the manufacture of cannabinoid containing cigarettes is lacking. The numerous cannabis strains with variable cannabinoid content, differences in cultivation methods and variability in assembly associated with hand-rolled cannabis cigarettes makes consistent cannabinoid inhalation dosing challenging. To address the growing need for standardization in the manufacture of cannabis cigarettes we developed a process for the production of filtered CN using machine-rolled tobacco cigarette equipment. The processed CN packing density, particle size distribution and curing procedures were designed to produce filtered CN that were identical in appearance and qualitatively similar in combustion properties to market-leading filtered commercial tobacco cigarettes. Quality control procedures were implemented to assure consistency in the manufacturing process and minimize variability associated with cigarette production such as inconsistencies in packing density, particle size, and combustion rate of mainstream smoke. Passive inverted smoldering assessment indicated that CN cigarettes burned at a faster rate compared to commercial filtered tobacco cigarettes of similar density. Overall, it is expected that machine-rolled standardized cannabis cigarettes with control over filler particle sizes, packing density and smoldering rates will contribute to making inhalation dosing of cannabis cigarettes more effective for therapeutic use.

Current Status and Future of Cannabis Research

Cannabis sativa has a long history of medicinal use and contains phytocannabinoids that demonstrate therapeutic activity in preclinical models of numerous disease states. Widespread clinical use of cannabis has preceded the evidence base. Randomized controlled trials are needed to understand the safety, efficacy, and optimal dosages of standardized cannabis preparations. In addition to regulatory and legal challenges,certain botanical and pharmacologic factors that complicate the collection and interpretation of clinical data on the efficacy of cannabinoid therapies are reviewed.

Assessment of cannabis use disorders: a systematic review of screening and diagnostic instruments.

Cannabis use and misuse have become a public health problem. There is a need for reliable screening and assessment tools to identify harmful cannabis use at an early stage. We conducted a systematic review of published instruments used to screen and assess cannabis use disorders. We included papers published until January 2013 from seven different databases, following the PRISMA guidelines and a predetermined set of criteria for article selection. Only tools including a quantification of cannabis use and/or a measurement of the severity of dependence were considered. We identified 34 studies, of which 25 included instruments that met our inclusion criteria: 10 scales to assess cannabis use disorders, seven structured interviews, and eight tools to quantify cannabis use. Both cannabis and substance use scales showed good reliability and were validated in specific populations. Structured interviews were also reliable and showed good validity parameters. Common limitations were inadequate time-frames for screening, lack of brevity, undemonstrated validity for some populations (e.g., psychiatric patients, female gender, adolescents), and lack of relevant information that would enable routine use (e.g., risky use, regular users). Instruments to quantify consumption did not measure grams of the psychoactive compounds, which hampered comparability among different countries or regions where tetrahydrocannabinol concentrations may differ. Current instruments available for assessing cannabis use disorders need to be further improved. A standard cannabis unit should be studied and existing instruments should be adapted to this standard unit in order to improve cannabis use assessment.

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol

PurposeColon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. MethodsProliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [3H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. ResultsCBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. ConclusionsCBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.

An exploratory study of cannabis withdrawal among Indigenous Australian prison inmates: study protocol

IntroductionCannabis use and dependence is a serious health and criminal justice issue among incarcerated populations internationally. Upon abrupt, enforced cessation of cannabis, prisoners may suffer irritability and anger that can...

Non-Δ9tetrahydrocannabinol phytocannabinoids stimulate feeding in rats

Cannabinoid type 1 receptor-mediated appetite stimulation by Δ⁹tetrahydrocannabinol (Δ⁹THC) is well understood. Recently, it has become apparent that non-Δ⁹THC phytocannabinoids could also alter feeding patterns. Here, we show definitively that non-Δ⁹THC phytocannabinoids stimulate feeding. Twelve male, Lister-Hooded rats were prefed to satiety prior to administration of a standardized cannabis extract or to either of two mixtures of pure phytocannabinoids (extract analogues) comprising the phytocannabinoids present in the same proportions as the standardized extract (one with and one without Δ⁹THC). Hourly intake and meal pattern data were recorded and analysed using two-way analysis of variance followed by one-way analysis of variance and Bonferroni post-hoc tests. Administration of both extract analogues significantly increased feeding behaviours over the period of the test. All three agents increased hour-one intake and meal-one size and decreased the latency to feed, although the zero-Δ⁹THC extract analogue did so to a lesser degree than the high-Δ⁹THC analogue. Furthermore, only the analogue containing Δ⁹THC significantly increased meal duration. The data confirm that at least one non-Δ⁹THC phytocannabinoid induces feeding pattern changes in rats, although further trials using individual phytocannabinoids are required to fully understand the observed effects.

Quantifying cannabis use with the Timeline Followback approach: A psychometric evaluation

BackgroundIn the absence of a standardized cannabis unit, self-report instruments are inadequate for accurate quantification of cannabis use. The study extends the feasibility of using a cannabis substitute to reliably and validly measure quantity of cannabis use. MethodNinety-eight adult Australian cannabis users (M age=27.98, SD=11.10; 65.31% male) completed a 90-day Timeline Followback interview regarding their cannabis use, utilizing the cannabis substitute Marijuanilla to report on quantity of use. Ninety-two of these individuals completed the interview at two time-points, and 56 of these participants had collaterals corroborate their cannabis use reports. ResultsInter-rater reliability was excellent, while test–retest reliability was good to excellent. Intra-class correlation coefficients between participant and collateral reports, while similar to previous research, were unacceptable. Quantity of cannabis use statistically significantly added to frequency of use in predicting cannabis problems and dependence severity. Concurrent and discriminant validity were established with single-item and positive impression management measures, respectively. In addition, Marijuanilla appeared similar to one specimen of street seized cannabis, but not to two others. Importantly, participants’ cravings to use cannabis did not increase as a result of using the cannabis substitute to report on their cannabis use. ConclusionsThese data suggest that utilizing Marijuanilla to facilitate the reporting of grams of cannabis use may be reliable and valid; however, such comprehensive assessment may only be necessary for clinical trials and epidemiological studies, which rely on precise estimates of cannabis use.

Association between a cannabinoid receptor gene ( CNR1) polymorphism and cannabinoid-induced alterations of the auditory event-related P300 potential

Numerous studies demonstrated a close relationship between cannabis abuse and schizophrenia with similar impairments in cognitive processing, particularly in P300 generation. Recently, an (AAT) n triplet repeat polymorphism within the cannabinoid receptor gene CNR1 has been found to be associated with both schizophrenia and substance dependence, and to modulate the P300 potential. As previously reported, both acute oral Δ 9-tetrahydrocannabinol (Δ 9-THC), the main psychoactive constituent of cannabis, and standardized cannabis extract containing Δ 9-THC and cannabidiol (CBD) revealed a significant reduction of P300 amplitudes in healthy subjects but did not show any differences among each other. The aim of this study was to investigate whether the (AAT) n polymorphism differentially modulates the effects of Δ 9-THC and cannabis extract on P300 generation in 20 healthy volunteers during an auditory choice reaction task. For the >10/>10 genotype, there was a significant decrease of P300 amplitude as well as a significant prolongation of P300 latency under pure Δ 9-THC but not under cannabis extract. Moreover, we found a significant correlation between the number of AAT repeats and P300 variables for the Δ 9-THC condition. Our data thus indicate that the CNR1 gene seems to be involved in the regulation of the P300 wave as a marker of selective attention and working memory. Moreover, it appears that variations within CNR1 may differentially alter the sensitivity to the acute effects of cannabinoids on P300 generation in healthy subjects.

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy‐induced nausea and vomiting

Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.