Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders. The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies. A systematic search was performed in PubMed, Embase and Cochrane library for articles published in English between January 1, 2000 and October 25, 2019. The search terms used were related to cannabis and CBD in adults. We identified 25 studies (927 patients; 538 men and 389 women), of which 22 studies were controlled clinical trials (833 patients) and three were observational designs (94 patients) from five countries. Formulations, dose and dosage schemes varied significantly between studies. Varying effects were identified from the randomized controlled trials (RCTs), more apparent effects from non-RCTs and minor safety issues in general. From the controlled trials, we identified anxiolytic effects with acute CBD administration, and therapeutic effects for social anxiety disorder, psychotic disorder and substance use disorders. In general, studies were heterogeneous and showed substantial risks of bias. Although promising results have been identified, considerable variation in dosage schemes and route of administration were employed across studies. There was evidence to support single dose positive effect on social anxiety disorder, short medium-term effects on symptomatic improvement in schizophrenia and lack of effect in the short medium-term on cognitive functioning in psychotic disorders. Overall, the administration was well tolerated with mild side effects.
Rationale: While cannabis-based medicinal products have been shown to be effective for numerous neurological and psychiatric disorders, the evidence base regarding their adverse cognitive effects is poorly understood. The cannabinoid 1 receptor modulates memory performance via intracellular and extracellular mechanisms that alter synaptic transmission and plasticity. While previous literature has consistently shown that chronic cannabis users exhibit marked cognitive impairments, mixed findings have been reported in the context of placebo-controlled experimental trials. It is therefore unclear whether these compounds inherently alter cognitive processes or whether individuals who are genetically predisposed to use cannabis may have underlying cognitive deficits. OBJECTIVE: We conducted a meta-analysis to investigate the effects of full and partial cannabinoid 1 receptor (CB1R) agonists, antagonists, and negative allosteric modulators on non-spatial and spatial memory. METHODS: In accordance with the PRISMA guidelines, the EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining the effects of CB1R agonists, antagonists, and negative allosteric modulators on memory performance. RESULTS: We systematically reviewed 195 studies investigating the effects of cannabinoid compounds on memory. In humans (<i>N</i> = 35 studies, comprising <i>N</i> = 782 subjects), delta-9-tetrahydrocannabinol (THC) (1.5–5 mg/kg) relative to placebo impaired performance on non-spatial memory tests, whereas only high THC doses (67 mg/kg) impaired spatial memory. Similarly, THC (0.2–4 mg/kg) significantly impaired visuospatial memory in monkeys and non-human primates (<i>N</i> = 8 studies, comprising <i>N</i> = 71 subjects). However, acute THC (0.002–10 mg/kg) had no effect on non-spatial (N = 6 studies, comprising 117 subjects; <i>g</i> = 1.72, 95% confidence interval (CI) −0.18 to 3.63, <i>p</i> = 0.08) or spatial memory (9 studies, comprising 206 subjects; <i>g</i> = 0.75, 95% confidence interval (CI) −1.09 to 2.58, <i>p</i> = 0.43). However, acute, full CB1R agonists significantly impaired non-spatial memory (<i>N</i> = 23 studies, 519 subjects; <i>g</i> = −1.39, 95% CI—2.72 to—0.06, <i>p</i> = 0.03). By contrast, the chronic administration of CB1R agonists had no effect on non-spatial memory (<i>N</i> = 5 studies, comprising 146 subjects; <i>g</i> = −0.05, 95% confidence interval (CI) −1.32 to 1.22, <i>p</i> = 0.94). Moreover, the acute administration of CB1R antagonists had no effect on non-spatial memory in rodents (<i>N</i> = 9 studies, <i>N</i> = 149 subjects; <i>g</i> = 0.40, 95% CI −0.11 to 0.92, <i>p</i> = 0.12). CONCLUSIONS: The acute administration of THC, partial CB1R agonist, significantly impaired non-spatial memory in humans, monkeys, and non-human primates but not rodents. However, full CB1R agonists significantly impaired non-spatial memory in a dose-dependent manner but CB1R antagonists had no effect on non-spatial memory in rodents. Moreover, chronic THC administration did not significantly impair spatial or non-spatial memory in rodents, and there is inconclusive evidence on this in humans. Our findings highlight species differences in the effects of cannabinoid compounds on memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
En 2010, una revisión de Hazekamp y Grotenhermen abarcó los ensayos clínicos controlados de los años 2006-2009 sobre los medicamentos a base de cannabis, que siguieron el ejemplo de la revisión de Ben Amar (2006). La revisión actual informa sobre los datos clínicos más recientes disponibles de 2010-2014. Se realizó una búsqueda sistemática en la base de datos científica de PubMed, centrada en estudios clínicos que fueron aleatorizados, doble ciego y controlados con placebo. Las palabras clave utilizadas fueron cannabis, marijuana, marihuana, hachís, cannabinoides, tetrahidrocannabinol, THC, CBD, dronabinol, Marinol, nabilona, Cannador, nabiximoles y Sativex. Para la selección final, sólo se mantuvieron ensayos clínicos controlados adecuadamente. Se excluyeron los estudios abiertos, excepto si eran una continuación directa de un estudio discutido aquí. Se identificaron treinta y dos estudios controlados que evaluaron los efectos terapéuticos de los cannabinoides. Para cada ensayo clínico se describen el país donde se realizó el proyecto, el número de pacientes evaluados, el tipo de estudio y las comparaciones realizadas, los productos y las dosis utilizadas, su eficacia y sus efectos adversos. Sobre la base de los resultados clínicos, los cannabinoides presentan un potencial terapéutico interesante principalmente como analgésicos en el dolor neuropático crónico y espasticidad en la esclerosis múltiple. Pero una serie de otras indicaciones también parecen prometedoras. CBD (cannabidiol) emerge como otro valioso canabinoide para fines terapéuticos además de THC. Palabras clave: cannabinoides, cannabis, potencial terapéutico, ensayo clínico controlado, eficacia, seguridad, cannabidiol
Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders. The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies. A systematic search was performed in PubMed, Embase and Cochrane library for articles published in English between January 1, 2000 and October 25, 2019. The search terms used were related to cannabis and CBD in adults. We identified 25 studies (927 patients; 538 men and 389 women), of which 22 studies were controlled clinical trials (833 patients) and three were observational designs (94 patients) from five countries. Formulations, dose and dosage schemes varied significantly between studies. Varying effects were identified from the randomized controlled trials (RCTs), more apparent effects from non-RCTs and minor safety issues in general. From the controlled trials, we identified anxiolytic effects with acute CBD administration, and therapeutic effects for social anxiety disorder, psychotic disorder and substance use disorders. In general, studies were heterogeneous and showed substantial risks of bias. Although promising results have been identified, considerable variation in dosage schemes and route of administration were employed across studies. There was evidence to support single dose positive effect on social anxiety disorder, short medium-term effects on symptomatic improvement in schizophrenia and lack of effect in the short medium-term on cognitive functioning in psychotic disorders. Overall, the administration was well tolerated with mild side effects.
