Cannabidiol Content Research Articles

Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ9tetrahydrocannabinol

Background and PurposeRecent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ9tetrahydrocannabinol (THC) content. Self‐selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship.Experimental ApproachIn this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self‐Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg−1, i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg−1 CBD.Key ResultsCBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self‐Ordered Spatial Search task of working memory. CBD did not significantly reverse THC‐induced impairment of a progressive ratio or a rotating turntable task.Conclusions and ImplicationsThis study provides direct evidence that CBD can oppose the cognitive‐impairing effects of THC and that it does so in a task‐selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC‐containing therapeutic products may therefore help to ameliorate unwanted cognitive side‐effects.Linked ArticleThis article is commented on by Mechoulam and Parker, pp 1363–1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). “Known Provenance” samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

The prevalence and incidence of medicinal cannabis on prescription in The Netherlands

A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor's prescription. This study describes a retrospective database study of The Netherlands. Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003-2010. Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties. Five thousand five hundred forty patients were identified. After an initial incidence of about 6/100,000 inhabitants/year in 2003 and 2004, the incidence remained stable at 3/100,000/year in 2005-2010. The prevalence rate ranged from 5 to 8 per 100,000 inhabitants. Virtually all patients used some form of prescription medication in the 6months preceding start of cannabis use, most particularly psycholeptics (45.5%), analgesics (44.3%), anti-ulcer agents (35.9%) and NSAIDs (30.7%). We found no significant association between use of medication of common indications for cannabis (pain, HIV/AIDS, cancer, nausea, glaucoma) and variety of cannabis used. This is the first nationwide study into the extent of prescription of medicinal cannabis. Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol (THC) and cannabidiol (CBD), no differences in choice of variety was found associated with indication.

Effects of abscisic acid on content and biosynthesis of terpenoids in Cannabis sativa at vegetative stage

The influence of abscisic acid (ABA) on plastidial and cytosolic terpenoids and on two key enzymes for terpenoid biosynthesis was determined in vegetative stage of Cannabis sativa L. Low concentration of ABA (1 μM) increased 1-deoxy-D-xylulose 5-phosphate synthase (DXS) activity in treated plants in comparison to control plants. The amounts of chlorophyll a and carotenoids increased in response to ABA treatment but chlorophyll b content declined. The accumulation of α-tocopherol was stimulated only by 10 μM ABA. The ABA-treated plants showed a decline in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity which was followed by a decrease in squalene and phytosterol content. ABA also decreased tetrahydrocannabinol (THC) and cannabidiol (CBD) contents. The essential oil had higher ratios of monoterpenes to sesquiterpenes as ABA-treated plants had less numbers of sesquiterpenes in comparison with control plants. Influence of ABA on the amounts of sesquiterpenes was different, some of them showed decrease of content and others increase of content.

Effects of abscisic acid on content and biosynthesis of terpenoids in Cannabis sativa at vegetative stage

The influence of abscisic acid (ABA) on plastidial and cytosolic terpenoids and on two key enzymes for terpenoid biosynthesis was determined in vegetative stage of Cannabis sativa L. Low concentration of ABA (1 &mu;M) increased 1-deoxy-D-xylulose 5-phosphate synthase (DXS) activity in treated plants in comparison to control plants. The amounts of chlorophyll a and carotenoids increased in response to ABA treatment but chlorophyll b content declined. The accumulation of &alpha;-tocopherol was stimulated only by 10 &mu;M ABA. The ABA-treated plants showed a decline in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity which was followed by a decrease in squalene and phytosterol content. ABA also decreased tetrahydrocannabinol (THC) and cannabidiol (CBD) contents. The essential oil had higher ratios of monoterpenes to sesquiterpenes as ABA-treated plants had less numbers of sesquiterpenes in comparison with control plants. Influence of ABA on the amounts of sesquiterpenes was different, some of them showed decrease of content and others increase of content.

Cannabis with high cannabidiol content is associated with fewer psychotic experiences

ObjectiveCannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to Δ 9-tetrahydrocannabinol (Δ 9-THC). An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users. MethodsIn a web-based cross-sectional study we obtained detailed information about cannabis use and subclinical psychiatric experiences using the Community Assessment of Psychic Experiences (CAPE). Different types of cannabis (i.e. marijuana, hashish etc.) have distinctive proportions of Δ 9-THC and cannabidiol. Since average concentrations of Δ 9-THC and cannabidiol in the most popular types of cannabis sold on the Dutch market are annually measured, we were able to estimate exposure to Δ 9-THC and cannabidiol. ResultsWe included 1877 subjects (mean age 23, SD 6.0) who used the same type of cannabis in the majority of the occasions (in >60% of occasions). We found a significant inverse relationship (F(1,1877): 14.577, p<0.001) between cannabidiol content and self-reported positive symptoms, but not with negative symptoms or depression. The estimated effect size of cannabidiol content was small. ConclusionAlthough the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.

Influence of agroclimatic conditions on content of main cannabinoids in industrial hemp (Cannabis sativa L.)

In a six-year field experiment eight industrial hemp varieties were examined for ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD) contents. The study analyzed the influence of growing degree days (GDD), soil temperature at 5 cm, air humidity, and growing season precipitation on the levels of the main cannabinoids in this crop. Agroclimatic conditions do not influence THC and CBD contents in industrial hemp in the same way. THC synthesis and accumulation are under the significant positive influence of GDD and air humidity and under the negative influence of precipitation, while soil temperature at 5 cm has no significant effect on it. Soil temperature at 5 cm has a significant positive effect on the CBD content, as do GDD. Precipitation has a negative influence on the CBD content of industrial hemp, while air humidity has no influence on it.

Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study

The two main constituents of cannabis, cannabidiol and Δ(9)-tetrahydrocannabinol (THC), have opposing effects both pharmacologically and behaviourally when administered in the laboratory. Street cannabis is known to contain varying levels of each cannabinoid. To study how the varying levels of cannabidiol and THC have an impact on the acute effects of the drug in naturalistic settings. Cannabis users (n = 134) were tested 7 days apart on measures of memory and psychotomimetic symptoms, once while they were drug free and once while acutely intoxicated by their own chosen smoked cannabis. Using an unprecedented methodology, a sample of cannabis (as well as saliva) was collected from each user and analysed for levels of cannabinoids. On the basis of highest and lowest cannabidiol content of cannabis, two groups of individuals were directly compared. Groups did not differ in the THC content of the cannabis they smoked. Unlike the marked impairment in prose recall of individuals who smoked cannabis low in cannabidiol, participants smoking cannabis high in cannabidiol showed no memory impairment. Cannabidiol content did not affect psychotomimetic symptoms, which were elevated in both groups when intoxicated. The antagonistic effects of cannabidiol at the CB(1) receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC. In terms of harm reduction, users should be made aware of the higher risk of memory impairment associated with smoking low-cannabidiol strains of cannabis like 'skunk' and encouraged to use strains containing higher levels of cannabidiol.

Effect of cannabis on pentobarbital-induced sleeping time and pentobarbital metabolism in the rat

The effects of two cannabis extracts with different cannabinoid compositions, as well of as pure Δ 1-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), on pentobarbital metabolism were studied in the rat. Extract I, with high proportions of CBN and CBD relative to THC, when given by gavage 21·5, 40 or 63 hr before pentobarbital (30 mg/kg, i.p.), prolonged the sleeping time by 53, 42 and 21 per cent respectively. This effect was paralleled by decreases in the rate of disappearance of [ 14C]pentobarbital from the blood, and of pentobarbital metabolism by liver microsomal preparations in vitro. Extract II, with low relative proportions of CBN and CBD, did not have any significant effect on penobarbital metabolism or sleeping time. CBD alone, in the same dose as that given in Extract I, had very similar effects, while a dose of CBD equivalent to that given in Extract II had no effect. THC, CBN and CBD added to normal rat liver microsomes in vitro inhibited pentobarbital metabolism competitively, CBD being a much more potent inhibitor than THC and CBN. The CBD content may, therefore, be a significant factor in interactions between marijuana and other drugs.

Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism

Summary Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30–32° C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4‐fold at 500 mg/kg. Under these conditions, ether sleeping time was not prolonged. Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome‐rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation. Δ1‐Tetrahydrocannabinol (Δ1‐THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water‐soluble fractions of the extract were inactive on pentobarbitone sleep. Cannabidiol was strongly active by both tests; in vivo 39·8 μm/kg (12·5 mg/kg) prolonged sleep by 190%, and in vitro 12·7 μm inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract. The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected. It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.

A STUDY OF INFRA–RED SPECTRA OF CANNABIS RESIN

Various types of cannabis resin exhibit marked and characteristic differences in their infra–red spectra over the region 700–1300 cm–1. The observed absorption characteristics are explained by the differences in the content of cannabidiolic acid, cannabidiol, tetrahydrocannabinols and cannabinol in the samples examined. The absorption curves and particularly the value T890–T1130 offer the possibility to examine the progress of the phytochemical interconversion of cannabinols („ripening” process) as well as to estimate the type and the chemical composition of the resin.