Cannabidiol for the treatment of autism spectrum disorder: hope or hype?

RATIONALE: Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorders in prevalence, morbidity, and impact on society. It is usually accompanied by attention deficit hyperactivity disorder, anxiety, depression, sleep disorders, and epilepsy. The treatment of ASD has low efficacy, possibly because it has a heterogeneous nature, and its neurobiological basis is not clearly understood. Drugs such as risperidone and aripiprazole are the only two drugs available that are recognized by the Food and Drug Administration, primarily for treating the behavioral symptoms of this disorder. These drugs have limited efficacy and a high potential for inducing undesirable effects, compromising treatment adherence. Therefore, there is great interest in exploring the endocannabinoid system, which modulates the activity of other neurotransmitters, has actions in social behavior and seems to be altered in patients with ASD. Thus, cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system. OBJECTIVES: Review the preclinical and clinical data supporting CBD's potential as a treatment for the symptoms and comorbidities associated with ASD, as well as discuss and provide information with the purpose of not trivializing the use of this drug.

Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli.

This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.

Biological bases for a possible effect of cannabidiol in Parkinson's disease

Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson's disease.

BACKGROUND: Cannabidiol (CBD) is one of the main components of Cannabis sativa and has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson's disease (PD). This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measures and tremors induced by a Simulated Public Speaking Test (SPST) in individuals with PD. METHODS: A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables. RESULTS: There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer. CONCLUSION: Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.

Biological bases for a possible effect of cannabidiol in Parkinson's disease.

Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana. Objectives: The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry. Methods: A non-systematic search was performed for studies dealing with therapeutic applications of CBD, especially performed by Brazilian researchers. Results: CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson. Discussion: CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.

Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats.

Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection. Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg). Conditioned place preference (CPP) paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg) inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 µL) injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 µL) did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness. Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. In addition, the study gives further support to the notion that the sensorial and affective dimensions of pain may be differentially modulated by CBD.

Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia.

Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period.

Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial.

INTRODUCTION: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. METHODS: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). RESULTS: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). CONCLUSIONS: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.

Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.

Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: the SHR strain.

Studies have suggested that the endocannabinoid system is implicated in the pathophysiology of schizophrenia. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs display hyperlocomotion - reverted by atypical and typical antipsychotics. These results suggest that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia and the effects of potential drugs with an antipsychotic profile. The aim of this study was to investigate the effects of WIN55-212,2 (CB1/CB2 agonist), ACEA (CB1 agonist), rimonabant (CB1 inverse agonist), AM404 (anandamide uptake/metabolism inhibitor), capsaicin (agonist TRPV1) and capsazepine (antagonist TRPV1) on the social interaction and locomotion of control animals (Wistar rats) and SHRs. The treatment with rimonabant was not able to alter either the social interaction or the locomotion presented by Wistar rats (WR) and SHR at any dose tested. The treatment with WIN55-212,2 decreased locomotion (1mg/kg) and social interaction (0.1 and 0.3mg/kg) of WR, while the dose of 1mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3mg/kg) and decreased (1mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5mg/kg), and decreased social interaction and increased locomotion in WR (1mg/kg). The treatment with capsaicin (2.5mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5mg/kg) and WR (0.5mg/kg and 2.5mg/kg). In addition, capsazepine (5mg/kg) decreased locomotion of both strains and increased (5mg/kg) and decreased (10mg/kg) social interaction of WR. Our results indicate that the schizophrenia-like behaviors displayed by SHR are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia.

Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature.

BACKGROUND: Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. OBJECTIVE: To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. METHODS: A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. RESULTS: The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. CONCLUSION: Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.

Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study.

Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions. Identical 10 mg THC, 600 mg CBD, and placebo capsules were allocated in a balanced double-blinded pseudo-randomized crossover design. Plasma levels of each substance, physiological parameters, and measures of psychopathology were taken at baseline and at regular intervals following ingestion of substances. Volunteers listened passively to words read and viewed a radial visual checkerboard in alternating blocks during fMRI scanning. Administration of THC was associated with increases in anxiety, intoxication, and positive psychotic symptoms, whereas CBD had no significant symptomatic effects. THC decreased activation relative to placebo in bilateral temporal cortices during auditory processing, and increased and decreased activation in different visual areas during visual processing. CBD was associated with activation in right temporal cortex during auditory processing, and when contrasted, THC and CBD had opposite effects in the right posterior superior temporal gyrus, the right-sided homolog to Wernicke's area. Moreover, the attenuation of activation in this area (maximum 61, -15, -2) by THC during auditory processing was correlated with its acute effect on psychotic symptoms. Single doses of THC and CBD differently modulate brain function in areas that process auditory and visual stimuli and relate to induced psychotic symptoms.

Adhesio interthalamica alterations in schizophrenia spectrum disorders: A systematic review and meta-analysis.

Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher prevalence of an absent adhesio interthalamica (AI; also known massa intermedia), a gray matter junction that is present between the two thalami in approximately 80% of healthy subjects. In this meta-analytic review, we describe and discuss the main AI MRI findings in schizophrenia spectrum disorders (SSDs) to date. The MEDLINE and ISI Web of Knowledge databases were searched up to December 2010, for studies that used MRI to assess AI in patients with SSD and controls. From fourteen potential reports, eleven were eligible to be part of the current review. These studies included 822 patients with SSD and 718 healthy volunteers. There was a large degree of variability in the MRI methods they employed. Patients with SSD had a higher prevalence of absent AI than healthy volunteers (odds ratio = 1.98; 95% confidence interval 1.33-2.94; p = 0.0008). This association was evident in both male and female SSD subjects, and there was no evidence that the prevalence was related to age or duration of illness. The significance of the absence of an AI for SSD may be clarified by studies in large, longitudinal community-based samples using standardized methods.

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania.

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by D-amphetamine (D-AMPH). In the first model (reversal treatment), rats received saline or D-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or D-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology.

Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Delta-9-tetrahydrocannabinol. Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Delta-9-THC.