Cannabis is a family of plants with two primary classifications popularity of CBD across the globe, hemp is also used to produce a wide. It is the primary non-psychoactive chemical of the cannabis plant, beneficial in It is the higher concentration that makes CBD beneficial in the. What makes someone more susceptible to its negative effects is not yet known, . The most researched compounds of the plant are dTHC and CBD and.
Plant How and the CBD THC Produces
Sativa- dominant strains are usually taller and have thin leaves with a pale green colour. Due to its higher THC content, C. It is a complex plant with about chemical entities, of which more than 60 are cannabinoid compounds [ Dewey, ]. In the plant, cannabinoids are synthesized and accumulated as cannabinoid acids, but when the herbal product is dried, stored and heated, the acids decarboxylize gradually into their proper forms, such as CBD or dTHC [ De Meijer et al.
Originally it was thought that CBD was the metabolic parent to dTHC, but it was later found that its biosynthesis occurs according to a genetically determined ratio [ Russo and Guy, ]. Even though the chemical structures of all four compounds are similar, their pharmacological effects can be very different. The most researched compounds of the plant are dTHC and CBD and therefore we will mainly focus on these two compounds and their differences.
Natural compounds of the cannabis plant are also referred to as phytocannabinoids of which dTHC is the main psychoactive ingredient and has been widely researched both in animals and humans.
It characteristically produces, in a dose-dependent manner, hypoactivity, hypothermia, spatial and verbal short-term memory impairment [Hayakawa et al. However, the second major compound, CBD, does not affect locomotor activity, body temperature or memory on its own. The available research indicates that the main two compounds, dTHC and CBD, whilst having similar effects in certain domains, also have almost opposite effects to one another in other aspects [ Carlini et al.
Table 1 summarizes the varying effects of these two compounds. Effects of tetrahydrocannabinol and cannabidiol, adapted and updated from Russo and Guy . In fact the different and opposing effects of the main two compounds of the plant were noticed in some early studies. In a double-blind study with 40 healthy volunteers, Karniol and colleagues orally administered dTHC and CBD and the mixtures of the two together, whilst pulse rate, time production tasks and psychological reactions were measured [ Karniol et al.
Whilst dTHC alone increased pulse rate, disturbed time tasks and induced strong psychological reactions in the subjects, CBD alone provoked no such effects. CBD also decreased the anxiety component of dTHC effects in such a way that the subjects reported more pleasurable effects. Most recently there have been a number of drug challenge studies with sound methodologies examining the effects of both of these compounds.
Our group carried out a number of double-blind, pseudo-randomized studies on healthy volunteers who had previous minimal exposure to cannabis. All participants were administered 10 mg of dTHC, mg of CBD and placebo flour in three different functional magnetic resonance imaging sessions while performing a response inhibition task, a verbal memory task, an emotional task viewing fearful faces and an auditory and visual sensory processing task. The overall concluding results showed that dTHC and CBD had different behavioural effects and also, at times, opposing brain activation in various regions [ Borgwardt et al.
DTHC caused transient psychotic symptoms and increased the levels of anxiety, intoxication and sedation, whilst CBD had no significant effect on behaviour or these parameters. In relation to the imaging data, during the response inhibition task, relative to placebo, dTHC attenuated the engagement of brain regions that normally mediate response inhibition, whilst CBD modulated activity in regions not implicated with this task [ Borgwardt et al.
During the verbal learning and retrieval of word pair tasks, dTHC modulated activity in mediotemporal and ventrostriatal regions, whilst CBD had no such effect [ Bhattacharyya et al.
During an emotional processing task dTHC and CBD had clearly distinct effects on the neural, electrodermal and symptomatic response to fearful faces [ Fusar-Poli et al.
Our results suggest that the effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of dTHC may be related to effects in other brain regions.
During the auditory task, again these two compounds had opposite effects in the superior temporal cortex when subjects listened to speech and in the occipital cortex during visual processing [ Winton-Brown et al.
Our group also assessed whether pretreatment with CBD could prevent the acute psychotic symptoms induced by dTHC when six healthy volunteers were administered dTHC intravenously on two occasions, after placebo or CBD pretreatment [ Bhattacharyya et al. Both animal and human studies indicate that CBD has anxiolytic properties. In fact in a recent double-blind study carried out on patients with generalized social anxiety disorder, it was found that relative to placebo, CBD significantly reduced subjective anxiety and its effect was related to its activity on limbic and paralimbic areas as shown by single photon emission computed tomography [ Crippa et al.
CBD has also been proposed to have antipsychotic effects and is considered a potential antipsychotic medicine, particularly due its relatively low side-effect profile [ Zuardi et al.
Another interesting compound of the plant, dtetrahydrocannabivarin dTHCV , a novel CB1R antagonist, also exerts potentially useful actions in the treatment of epilepsy and obesity [ Pertwee, ; Izzo et al. A review of this compound, along with dTHC and CBD by Pertwee suggests that plant extractions of d - 9-THCV produces its antiobesity effects more by increasing energy expenditure than by reducing food intake [ Pertwee, ].
The author also points out that a medicine such as dTHCV, by simultaneously blocking CB1Rs and activating CB2Rs, may have potential for the management of disorders such as chronic liver disease and obesity, particularly when these are associated with inflammation. However, the CBD content was found to be extremely low in more recent times. More recently, a meta-analysis to assess the potency of cannabis from to was carried out.
From 21 case series covering a number of countries, a recent and consistent worldwide increase in cannabis potency was reported [ Cascini et al. These findings suggest that current trends for preferring higher THC content variants carry significant health risks, particularly to those who are susceptible to its harmful effects. Indeed, Morgan and colleagues carried out a study on current users, which included 66 daily and 54 recreational users, whose hair analyses revealed their THC and CBD amounts.
The study found that higher THC levels in hair in daily users were associated with increased depression and anxiety, as well as poorer prose recall and source memory [ Morgan et al.
However, higher CBD in hair was associated with lower psychosis-like symptoms and better recognition memory. In relation to people with psychosis, health risks are even higher with stronger variants of the plant. In a recent study of people with a first episode of psychosis, it was found that patients used higher-potency cannabis for longer durations and greater frequency compared with a healthy control group [ Di Forti et al.
As the stronger variants have been taking over the street market, there has been a surge of interest in studying the links between cannabis use and mental health problems.
The first to draw attention to such a link was a number of epidemiological studies and reviews, which pointed towards an association between the use of cannabis and the increased risk of developing a psychotic illness, in a dose-dependent manner [ Zammit et al.
A psychotic outcome is not the only diagnostic category which has been associated with cannabis use. Symptoms of depression and anxiety commonly coexist with cannabis use and lead to diagnostic dilemmas [ Nunes et al. Cannabis use can induce such symptoms, as well as be used secondary to a primary depressive illness [ Dakwar et al. As the majority of the studies have had psychotic illness as an outcome, in this section we will mainly be focusing on this diagnostic category. This is important as the strong THC variants of cannabis use have been increasing steeply, as have concerns on cannabis-related health risks, particularly for young people [ Hall and Degenhardt, ; Potter et al.
Recent epidemiological studies point towards a link between the use of cannabis and the development of a psychotic illness [ Zammit et al. Further evidence comes from a systematic review of longitudinal and population-based studies which show that cannabis use significantly increases the risk of development of a psychotic illness in a dose-dependent manner [ Moore et al.
The clinical picture of transient psychosis can be indistinguishable from a frank acute psychosis with delusions and hallucinations, except for its short duration. Evidently there is considerable variation in the effects of cannabis on individuals. The biological basis of this variable sensitivity is yet unclear. There have been a number of studies exploring which groups are more vulnerable to developing a psychotic outcome as a result of cannabis use [ van Os et al.
Findings so far indicate that the effect of cannabis use is much stronger in those with any predisposition for psychosis at baseline than in those without [ Henquet et al. Indeed, individuals with a predisposition to psychosis indicated by a positive family history of psychosis have been found to be particularly sensitive to the effects of cannabis [ McGuire et al.
Another indicator for a higher psychosis risk is the presence of subclinical psychotic features and again such individuals have been affected by a higher risk of developing a psychotic illness [ Henquet et al. Furthermore those who are at ultra high risk for psychosis have been reported to be more sensitive to the psychotogenic effects of cannabis compared with users in the general population [ Peters et al.
Because of the reported links between the schizotypal personality and schizophrenia, this type of personality disorder has come under scrutiny in examining the role of cannabis in producing psychotic symptoms. Indeed, it has been shown that people scoring high in schizotypy who use cannabis are more likely to have psychosis-like experiences at the time of use, together with unpleasant side effects [ Barkus et al.
This study has been replicated and it has been confirmed that those with schizotypal personality disorder carry a higher risk of experiencing psychotic symptoms with cannabis use [ Stirling et al. Most recently, another study has provided further support for a strong association between early cannabis use and the development of schizophrenia spectrum disorder symptoms [ Anglin et al.
The reported vulnerability factors mentioned here imply a strong genetic predisposition and there have been a number of studies looking particularly to specific genes which have been implicated in psychoses. The first such study was carried out by Caspi and colleagues [ Caspi et al.
In this longitudinal study, a specific susceptibility gene which has been linked to schizophrenia and bipolar disorder, catechol-O-methyltransferase COMT , was examined in a representative birth cohort followed to adulthood. The study found that carriers of the COMT valine allele were most likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis before the age of However, the number of people carrying this allele was small in this study.
Using a case-only design of people with schizophrenia, Zammit and colleagues re-examined this association but their findings did not support the different effects of cannabis use on schizophrenia according to variation in COMT [ Zammit et al. More recently, van Winkel and colleagues looked at the effects of recent cannabis use whilst examining single nucleotide polymorphisms in 42 candidate genes in patients with psychosis and their unaffected siblings [ van Winkel et al.
The authors found that genetic variation in serine-threonine protein kinase AKT1 may mediate both short- and long-term effects on psychosis expression associated with cannabis use. Further support for the possible involvement of the AKT1 gene comes from our study with healthy volunteers.
This study found that, during the encoding and recall conditions of the verbal memory task, the induction of psychotic symptoms by dTHC was correlated with the attenuated striatal and midbrain activation only in those who were G homozygotes of AKT1 and carriers of the 9-repeat allele dopamine transporter DAT1 [ Bhattacharyya et al.
Apart from schizotypal personality, the vulnerability factors to the psychotogenic effects of cannabis require replication. It is clear that further work needs to be carried out to explore the biological mechanisms which determine the vulnerability towards a psychotic outcome. During the last decade, endocannabinoid research has been one of the fastest growing fields in psychopharmacology, opening ways to discover new medicines for a wide variety of health problems, ranging from metabolic disorders, to glaucoma and schizophrenia.
The distribution of the endocannabinoid system in the brain is interesting as the very same brain areas are also implicated in psychoses, particularly in schizophrenia. Furthermore, complex and intricate involvement of this system with other neurotransmitters such as dopamine, GABA and glutamatergic systems may have implications for the development of a psychotic illness. Naturally, due to the recent and constant increase in the availability of higher THC content variants of cannabis around the world, there have been increasing concerns about the health risks, particularly for young people.
However, cannabis affects people differently and therefore it is important to understand what makes someone more at risk and how they differ compared with those who do not develop psychotic illness. Here we have provided an overview of the available information on the risk factors which may make an individual more at risk, such as predisposition to psychosis, schizotypal personality and certain susceptibility genes.
Finding groups who are vulnerable is particularly important so that they can be targeted for early preventative and therapeutic interventions. Such a search would also lead to the discovery of the biochemical mechanisms involved in cannabis and endocannabinoid research and ultimately to a better understanding of how the brain and the body functions. Thanks to Ethan Russo and Geoffrey W. Guy for providing the inspiration for Table 1.
Also thanks to Dr Sanem Atakan for her help with the editing of the first draft. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest statement: The author declare no conflicts of interest in preparing this article. National Center for Biotechnology Information , U. Journal List Ther Adv Psychopharmacol v. Author information Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Abstract Cannabis is a complex plant, with major compounds such as deltatetrahydrocannabinol and cannabidiol, which have opposing effects. Cannabis, deltatetrahydrocannabinol, cannabidiol, tetrahydrocannabivarin, endocannabinoids, individual sensitivity to cannabis. Introduction Cannabis is a complex plant with over chemical entities of which more than 60 of them are cannabinoid compounds, some of them with opposing effects.
Brief history of the biochemistry of the cannabis plant Even though cannabis has been used and cultivated by mankind for at least years [ Li, ] our current knowledge on its pharmacological properties is based on studies which have taken place only since the end of the nineteenth century.
Open in a separate window. Chemical structures of deltatetrahydrocannabinol and cannabidiol. Cannabinoid receptor system Another cornerstone in cannabinoid research was the identification of the specific binding sites of dTHC in the brain [ Devane et al. Cannabinoid 1 and 2 receptors CB1Rs are mainly in the brain, particularly in the substantia nigra, the basal ganglia, limbic system, hippocampus and cerebellum, but are also expressed in the peripheral nervous system, liver, thyroid, uterus, bones and testicular tissue [ Russo and Guy, ; Pagotto et al.
Functions of the endocannabinoid receptor system Available evidence indicates that we do not yet have a complete understanding of the varied functions of the endocannabinoid system, which is widely distributed both in the brain and in the peripheral system and most glands and organs in the body. Cannabis plant The cannabis plant has two main subspecies, Cannabis indica and Cannabis sativa , and they can be differentiated by their different physical characteristics.
Deltatetrahydrocannabinol and cannabidiol Natural compounds of the cannabis plant are also referred to as phytocannabinoids of which dTHC is the main psychoactive ingredient and has been widely researched both in animals and humans. Intersubject variation in response to the psychotogenic effects of cannabis About Proposed factors determining sensitivity to psychosis in cannabis users.
Sensitivity to psychosis as determined by: Possible sensitivity factors Study group Predisposition to psychosis Family history of psychotic illness McGuire et al. Conclusion During the last decade, endocannabinoid research has been one of the fastest growing fields in psychopharmacology, opening ways to discover new medicines for a wide variety of health problems, ranging from metabolic disorders, to glaucoma and schizophrenia. In its application, hemp and marijuana serve completely different purposes.
Marijuana, as it is widely known, is used for medicinal or recreational purposes. These include healthy dietary supplements, skin products, clothing, and accessories. Overall, hemp is known to have over 25, possible applications. Hemp and marijuana can be differentiated by looking at its appearance, makeup, and natural adaptability. Marijuana and hemp have noticeable and contrasting differences.
Marijuana looks contrastingly different from hemp. Few branches or leaves exist below the top part of the plant. When you observe the plants from afar, marijuana looks like a short fat bush. Hemp is typically skinnier and taller up to 20 ft.
At times, it almost looks like long ditchweed — hemp was actually found to grow among weeds in Nebraska. The main difference between the two is in its chemical composition, specifically in tetrahydrocannabinol THC.
Hemp, on the other hand, has a max THC level of 0. This threshold is heavily regulated in other countries that have legalized hemp. The environment in which hemp and marijuana are grown is strikingly different. Hemp is grown closely together as close as 4 inches apart and are typically grown in large multi-acre plots. It can also grow in variety of climates and its growth cycle is days. Unlike hemp, marijuana requires a carefully controlled, warm, and humid atmostphere for proper growth.
Its growth cycle only days. Medical cannabis also cannot be grown too close to each other. They are typically grown 6 feet apart. Hemp, on the other hand, is regulated to only contain a max THC level of 0.
Cannabis gets its high-inducing power from ancient viruses
Still, it's not all bad for hemp: The plant produces another lucrative compound called CBD, or cannabidiol. This nonpsychoactive molecule is the. The brother hemp plant produces hemp CBD, which has no buds and therefore primarily consists of CBD, with less than % THC. Products. Oil extracted from hemp plants can contain a lot of CBD, while oil from skunk plants will contain far more THC. THC produces the high that.