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This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as...
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... are hypothesised [4], but not yet cloned. Further research has elucidated analgesic mechanisms of cannabinoids, which include effects on numerous neurotransmitter systems and inter- actions with the endogenous opioid system. This paper will focus on the biochemical and clinical effects of two phytocannabinoids, D 9 - tetrahydrocannabinol (THC) (Fig. 1), the main psychoactive component of cannabis, and its non-psychoactive but highly physiologically relevant isomer, cannabidiol (CBD) (Fig. 1). While it was orig- inally thought that CBD was the metabolic parent to THC in the cannabis plant, rather, they are both bio- synthesised as THCA and CBDA from a cannabigerolic acid precursor ...
Context 2
... neurotransmitter systems and inter- actions with the endogenous opioid system. This paper will focus on the biochemical and clinical effects of two phytocannabinoids, D 9 - tetrahydrocannabinol (THC) (Fig. 1), the main psychoactive component of cannabis, and its non-psychoactive but highly physiologically relevant isomer, cannabidiol (CBD) (Fig. 1). While it was orig- inally thought that CBD was the metabolic parent to THC in the cannabis plant, rather, they are both bio- synthesised as THCA and CBDA from a cannabigerolic acid precursor (Fig. 2) according to genetically determined ratios [5], and then decarboxylated by heat or extraction to produce THC and CBD proper. It is ...
Similar publications
Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray (Sativex®) as add-on therapy to optimized standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity.
Methods: Sativex as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) was a two...
A large proportion of patients with multiple sclerosis (MS) have spasticity, which has a marked impact on their quality of life. Anecdotal evidence suggests a beneficial effect of cannabis on spasticity as well as pain. Recently, randomized, double-blind, placebo-controlled studies have confirmed the clinical efficacy of cannabinoids for the treatm...
Background
Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authoriz...
Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if...
The retinal pigment epithelium (RPE) interacts closely with the photoreceptors in fulfilling tasks of visual function. Since an understanding of the RPE function is essential for understanding the patho-mechanisms involved in vision loss, we explored the regulation of the vanilloid receptor subtype transient receptor potential TRPV2 channels that t...
Citations
... This suggests that these cannabinoids may have opposing effects on neurotransmitter systems, potentially including glutamate. Interestingly, CBD has been shown to antagonize some of the effects of THC, including intoxication and sedation (Russo and Guy 2006). This antagonism could involve modulation of glutamatergic transmission, although this is not explicitly stated. ...
Increased extracellular glutamate concentrations in the brain can cause neuronal injury. Cannabinoid use has been demonstrated to reduce extracellular glutamate levels in the brain in many animal models. However, there are no systematic reviews published evaluating the effect of cannabis on glutamate levels in the human brain. This review aimed to review studies that investigated the effect of cannabinoids on glutamate levels in the living human brain using neuroimaging methods and to provide evidence gathered from biomedical databases such as MEDLINE and EMBASE. Nine randomized controlled trials (RCTs) and ten observational studies met the eligibility criteria for this review. The articles included in the meta-analyses had a low risk of bias. Meta-analysis showed cannabis intake has no effects on the glutamate levels in human brain. However, there is limited evidence indicating that oral cannabidiol and cannabidivarin increased the glutamate/glutamine ratio in the basal ganglia while intravenous and vaped tetrahydrocannabinol increased glutamate in the basal ganglia. There is also some evidence showing oral cannabidiol increased glutamate in the hippocampus. Most of the observational studies in this review demonstrated a reduction in glutamate in the brain of chronic cannabis users. However, these findings are not definitive and will require further confirmations. This review suggests that acute cannabis administration may increase glutamate in the basal ganglia and hippocampus but not in other parts of the brain, while chronic cannabis use lead to a decrease in glutamate levels in some parts of the brain. The quality of this evidence is limited therefore further studies are needed.
... This recreational-user-driven increase in THC concentration has correlated with an increase in adverse effects among cannabis users [5]. High-THC concentration cannabis products are also marketed toward medical users, despite their potentially decreased efficacy and higher risk of adverse outcomes due to the biphasic properties of THC [5,7,8]. This loss of CBD in many popular strains is unfortunate due to the medicinal benefits of CBD itself and the suggested synergistic effect of all the chemical constituents of cannabis, known as the entourage effect [9,10]. ...
Introduction: Cannabis as a therapeutic agent is accessible to a growing number of people, though research suggests that many medical cannabis (MC) users undertake their cannabinoid therapy independently, without collaborating with a cannabis clinician or informing their primary care physician (PCP). The effects of medical collaboration or disclosure to PCP on outcomes of cannabinoid therapy is unknown. Researchers anticipate that those who collaborate with a cannabis clinician or disclose their medical cannabis use to their PCP will find MC to be more effective, will use less delta-9-tetrahydrocannabinol (THC) and more cannabidiol (CBD), and experience fewer side effects. Methods: Through an online survey, medical cannabis users reported their cannabis usage patterns, health outcomes, PCP awareness, and collaboration with cannabis clinicians. These responses were analyzed using a variety of statistical tests to search for differences in reported efficacy, specific cannabinoid, and side effects between different levels of medical professional involvement (n=988). Results: Patients who either worked with a cannabis clinician or reported their use to their PCP reported significantly higher efficacy (p < .001), and in the case of working specifically with a cannabis clinician, higher daily doses of cannabidiol were used (p < .001). CBD doses did not vary between those who had disclosed their MC use to their PCP and those who had not. There were no significant differences in THC doses or side effects identified between groups. Conclusion: The results indicated that undertaking cannabinoid therapy with PCP awareness or guidance from a cannabis clinician is associated with better outcomes.
... Recently, it has been proposed that CBD may act as a negative allosteric modulator of CB1 receptors [26]. When used in conjunction with THC, CBD reduces THC's psychoactivity and simultaneously increases clinical efficacy through its own properties [18,19,[32][33][34]. Furthermore, CBD also exhibits agonist activity for TRPV1 and GPR55 but acts as an antagonist of GPR19 and Cav2.2 channels, which participate in pain signaling and have an antinociceptive effect [18,20,32]. ...
Objective: Our objective is to provide an overview of the currently available scientific and clinical data supporting the use Cannabis and Cannabis-derived products for the treatment of chronic pain disorders. We also provide information for researchers, clinicians and patients to be better informed and understand the approach behind the recommendation of Cannabis as a potential adjuvant in the treatment/control of chronic pain. Background: Cannabis and its bioactive compounds have sparked interest in the field of pain treatment in spite of its controversial history and status as a controlled substance in many countries. With the increase in chronic pain, physicians and patients have started to look at alternative ways to treat pain aside from traditional treatments. One alternative is the use of cannabis to reduce/treat chronic pain disorders based on anecdotal accounts and the function of its phytocannabinoids. The two main cannabinoids in cannabis, THC and CBD, act on CB1 and CB2 receptors (in addition to several additional receptors). It is through these pleiotropic receptor interactions that these compounds elicit their biological function including the reduction of chronic pain. In this narrative review, we included the most recent evidence supporting the use of cannabis in the treatment of chronic pain disorders including chronic neuropathic pain, cancer-induced neuropathic pain, chronic musculoskeletal pain, and chronic headaches and migraines. Summary: Evidence suggests that cannabis and cannabinoids have an analgesic effect that arises from a combination of compounds and various receptor systems. These effects may be maximized with the use of a combination of cannabinoids. At the same time, the combination of cannabinoids helps to minimize the undesirable side effects of some cannabinoids such as the psychoactivity of THC. With these findings, further research is necessary to assess the analgesic properties of other cannabinoids like CBC and CBG, and their contributions to the reduction of pain.
... While both clinical and animal studies have shown that a combination of CBD and THC can be advantageous to treatments with one alone (59,60), the basis for this combinatorial effect is not well understood. Both CB1 and CB2 receptors are expressed in migraine-relevant regions of the nervous system (14,61) and meningeal immune cells (62), both of which may play a role in migraine (63). ...
Background
The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).
Methods
Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).
Results
In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.
Conclusions
A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.
... On the other hand, the non-psychoactive cannabinoid CBD possesses wider pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, neuroprotective, anxiolytic, and anticonvulsant (Appendino et al. 2011, Campos et al. 2016, and Sangiovanni 2019. Furthermore, the combination of THC and CBD enhances their therapeutic effects when compared to each of the cannabinoids alone (Russo andGuy 2006, andRusso 2011). ...
Abstract
Background Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated
with dose dependent nephrotoxicity limiting its use as anticancer agent.
Objective The current study aimed to investigate the nephroprotective efect of native Lebanese Cannabis sativa
in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.
Methods Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Can�nabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice
with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group
and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN),
and proteinuria were measured.
Results Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin
in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote
and restore the migratory capacity of podocytes in cisplatin-treated cells.
Interestingly, COE treatment improved urinary and serum parameters characterized by a signifcant decrease in serum
creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein
induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice
treated with cisplatin alone.
Conclusion Collectively, the aforementioned fndings indicate that COE could be a promising approach to protect
against cisplatin-induced nephrotoxicity.
Keywords Cannabis sativa, Cisplatin, Nephrotoxicity, Podocytes, Cisplatin-induced nephrotoxicity
... Certain mechanisms, like acting as an allosteric negative modulator of CB1 [47], can impact the bioactivity of THC [47]. This has prompted the suggestion that CBD functions as an entourage compound [48]. Additionally, CBD (3, Figure 1) can affect the pharmacokinetics of THC (2, Figure 1) by inhibiting some hepatic enzymes, such as those in the cytochrome P450 family, slowing the conversion of 2 into its more potent psychoactive metabolite, 11-OH-THC (22, Figure 6). ...
This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis “entourage effects” was conducted using the PRISMA model. Two research questions directed the review: (1) What are the physiological effects of terpenes and terpenoids found in cannabis? (2) What are the proven “entourage effects” of terpenes in cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity; however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa L. prevalent monoterpenes and the triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically; however, in combination with CBD, it did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxation; linalool as a sleep aid and to relieve exhaustion and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection; borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm any terpenes “entourage effects.”
... Accordingly, to address this knowledge gap, here, we investigated the profile of BG m 6 A methylome in host miRNAs during HIV/SIV infection and the potential effects of phytocannabinoids (THC and CBD) on the BG miRNA m 6 A methylome. We used a combination of THC and CBD (1:3) because findings from clinical studies have confirmed that THC is well-tolerated when administered in combination with CBD(30)(31)(32). Specifically, CBD diminished the adverse effects of THC, such as tachycardia, intoxication, and sedation, while preserving the beneficial effects of reduced muscle spasticity and neuroinflammation(30)(31)(32). ...
... We used a combination of THC and CBD (1:3) because findings from clinical studies have confirmed that THC is well-tolerated when administered in combination with CBD(30)(31)(32). Specifically, CBD diminished the adverse effects of THC, such as tachycardia, intoxication, and sedation, while preserving the beneficial effects of reduced muscle spasticity and neuroinflammation(30)(31)(32). ...
Background
Epitranscriptomic modifications modulate diverse biological processes like regulation of gene expression, abundance, location and function. N6-methyladenosine (m ⁶ A) methylation has been shown to regulate various diseases, including cancer and inflammation. While there is evidence that m ⁶ A modification is functionally relevant in neural development and differentiation, the role of m ⁶ A modification in HIV neuropathogenesis is unknown.
Methods
Here, we used anti-N6-methyladenosine (m ⁶ A) antibody immunoprecipitation and microarray profiling to identify m ⁶ A modifications in miRNAs in basal ganglia (BG) of Rhesus macaques (RMs) that were uninfected (VEH) and SIV-infected on combination anti-retroviral therapy (cART) and either VEH-treated (VEH/SIV/cART), or THC:CBD-treated (THC:CBD/SIV/cART). Ingenuity pathway analysis was conducted to understand the biological implications of miRNA m ⁶ A methylation in HIV neuropathogenesis. Finally, to understand the functional significance of m ⁶ A modifications in miRNAs, we overexpressed FAM-labeled wild-type or m ⁶ A-modified miR-194-5p in SCC-25 cells and determined its impact on the expression of its target, STAT1, an interferon-stimulated transcription factor known to drive persistent neuroinflammation in several neurodegenerative diseases.
Results
HIV/SIV infection promoted an overall hypomethylated miRNA m ⁶ A profile. While the overall hypomethylated m ⁶ A profile was not significantly impacted by THC:CBD, specific miRNAs predicted to target proinflammatory genes showed markedly reduced m ⁶ A methylation levels compared to the VEH-treated RMs. Additionally, specific BG tissue miRNAs bearing m ⁶ A epi-transcriptomic marks were transferred and detected in BG-derived extracellular vesicles. Mechanistically, the DRACH motif in the seed region of miR-194-5p was significantly m ⁶ A hypomethylated in THC:CBD/SIV/cART RMs. In SCC-25 cells, unlike wild-type miR-194-5p, transfected m ⁶ A-modified miR-194-5p mimics failed to downregulate STAT1 protein expression. Further, compared to VEH/SIV/cART RMs, THC:CBD administration significantly reduced m ⁶ A methylation of 44 miRNAs directly involved in regulating CNS network genes.
Conclusions
These results underscore the need for investigating the qualitative, and posttranscriptional modifications in RNA along with the more traditional, quantitative alterations in pathological conditions or in response to disease modifying treatments. Our findings indicate that m ⁶ A epitranscriptomic marks in the seed nucleotide region can impair miRNA function and that cannabinoids may preserve it by reducing m ⁶ A methylation levels. Finally, these findings provide a novel mechanistic (miRNA m ⁶ A hypomethylation) explanation underlying the anti-neuroinflammatory effects of phytocannabinoids in HIV/SIV infection.
... CB1Rs are primarily located in the brain, especially in regions like the substantia nigra, basal ganglia, limbic system, hippocampus, and cerebellum. They are also found in the peripheral nervous system, liver, thyroid, uterus, bones, and testicular tissue [Russo and Guy, 2006;Pagotto et al., 2006;Pertwee, 2006]. CB2Rs, meanwhile, are expressed mainly in immune cells, the spleen, gastrointestinal system, and to some extent in the brain and peripheral nervous system [Izzo, 2004;Pertwee, 2006]. ...
Cannabis is a complex plant containing over 400 chemical compounds, including key cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which exert opposing effects. The identification of these compounds has led to the exploration of the endocannabinoid system, a crucial neurotransmitter system widespread in the brain and body, responsible for various significant physiological functions. Recently, there has been a global increase in cannabis potency, raising health concerns. Epidemiological studies indicate a link between dose-dependent cannabis use and an elevated risk of persistent psychotic disorders. However, not all users experience adverse effects equally. The factors that contribute to individual susceptibility remain unclear, although emerging research suggests that genetics and personality traits may play a role. This article first examines the biochemical basis of cannabis and its two primary compounds, followed by a review of the factors that may explain the variability in individual responses to cannabis.
... Historical documents indicate that, around 2700 BC, the plant was used in China to treat various medical conditions, including constipation, pain, malaria and epilepsy, whereas India, its use dates back to before 1000 BC, being applied as hypnotic and anxiolytic in the treatment of anxiety, manias and hysteria (Matos, et al. 2017). At the beginning of the 20th century, extracts of Cannabis were sold in countries such as England, Germany and the United States to treat mental disorders, acting mainly as hypnotics and sedatives, since this plant contains several active compounds, of which delta-9-tetrahydrocannabinol (THC) is the best known for its psychoactive effects (Russo, 2006). Besides THC, the plant also contains cannabidiol (CBD), a non-psychotropic compound that can constitute up to 40% of the plant's extracts. ...
Objective: The aim of this study is to conduct a literature review of articles addressing the therapeutic use of cannabidiol for treating symptoms of epilepsy in children with congenital Zika virus syndrome. Theoretical Framework: Zika virus is an arbovirus transmitted by mosquitoes, first identified in Brazil in 2015. In severe cases, it can lead to Congenital Zika Virus Syndrome in fetuses, resulting in various neurological anomalies. Cannabidiol (CBD), found in Cannabis sativa, has emerged as a therapeutic alternative for treating symptoms, including epilepsy, but requires further clinical studies to confirm its efficacy and safety. Method: This is a literature review research, in which scientific articles on the therapeutic use of cannabidiol in children with epilepsy related to congenital Zika virus syndrome were selected. The research utilized electronic databases such as PubMed, Google Scholar, and Web of Science. Clinical studies evaluating the efficacy and safety of cannabidiol were included, while those without a control group or animal testing were excluded. Results and Discussion: The results obtained demonstrated that cannabidiol (CBD) is effective in reducing seizures in children with congenital Zika virus syndrome, improving their quality of life and motor skills. Its mechanisms of action suggest interaction with the endocannabinoid system, antioxidant action, and regulation of neurogenesis and synaptic plasticity. Studies have shown that CBD is generally safe and well-tolerated by these children. However, further research is necessary to fully understand its long-term effects and to determine the optimal dosage. Cannabidiol was shown to reduce seizures in 80% of children with congenital Zika virus syndrome, improving their quality of life and motor skills. It was well-tolerated, with no serious side effects. Research Implications: The results of this research are of great value for the health of children affected by the Zika virus. The need for more studies is evident, as the mechanisms of action of cannabidiol as a therapeutic treatment for this pathology require greater understanding. Nevertheless, it presents a promising therapeutic potential, requiring more research for better understanding and safe use. Originality/Value: This research contributes to the literature by gathering important information about the use of cannabidiol and its developments, with the aim of providing insights and assisting in the elucidation of possible further studies on the subject, thereby bringing positive impacts on public health, guiding clinical management, and contributing to the improvement of the quality of life of this affected population.
... 51 In this study, NAEs continued to increase, alongside a greater upturn of AEA, from the combination of CBD+Δ 9 -THC, leading us to speculate a positive contribution towards CBD-derived mechanisms occurs with the inclusion of Δ 9 -THC ('entourage effect'). 52 Though beyond this project's scope, prior evidence of CBD+Δ 9 -THC therapy supports analgesic efficacy 53 ; however, safety and tolerance of Δ 9 -THC remain debated. 54 Furthermore, single-dose administration of CBD+Δ 9 -THC through inhalation yielded no effect on eCB/NAE levels. ...
Background
The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual’s effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting.
Methods
Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ ⁹ -THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ ⁹ -THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration.
Results
CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (p corr <0.05) but not 600 mg dosage. Declining AEA was observed with Δ ⁹ -THC at 10 mg (−1.3-fold) and 20 mg (−1.4-fold) but restored to baseline levels by 160 min. CBD+Δ ⁹ -THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response.
Conclusion
CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ ⁹ -THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.
