He adds that if you find yourself in the middle of weed-induced anxiety, getting fresh air and moving around might help you metabolize the drug. Common symptoms of cannabis-induced anxiety disorder include severe panic attacks, obsessive and compulsive behavior, unexplained delirium, and. While cannabis is frequently used to treat anxiety, it can also cause it. Here is how to recognize, treat, and avoid the symptoms.
You see greater exacerbation of heart rate at higher doses. Remind yourself that this condition is not lasting but temporary. In due course, it will all be over. For many, weed-based anxiety involves a hefty dose of paranoia about other people. Because marijuana is a drug enjoyed in social settings, getting too stoned can lead to suspicions that your own friends resent you, or that you're somehow "ruining" their good time.
Cannabis is a perfect example. If environmental factors are contributing to your fear or stress, removing yourself from that context can help. Resist the idea that anyone hates you for obscure reasons of your own invention. In other words, this is a risk everyone runs with weed — but, Vandrey said, a "subset of people" are particularly vulnerable to it. In any case, rest assured that a weed-induced panic attack is not going on your permanent record, and will soon be forgotten by whoever happened to witness it.
The only judgment you face is your own. Who were you with? Of note, chronic consumption of cannabis has been hypothesized to exacerbate depressive or anxious manifestations, and reduce the therapeutic efficacy of anxiolytic agents [ , - ]; an interesting theoretical implication of this finding is that long-term exposure to cannabinoid agents may lead to profound alterations of synaptic plasticity and neurochemical homeostasis and alter the pathophysiological trajectory of anxiety and mood disorders.
Thus, while cannabis may be initially used as a self-therapy for certain anxiety disorders, the prolonged exposure to this substance in vulnerable individuals may in turn alter or aggravate the clinical course of these conditions and render the patients refractory to standard treatments.
The ability of cannabis to either exacerbate or attenuate emotional reactivity is highly influenced by numerous factors, including its chemotype, as well as the influence of genetic, developmental and contextual variables. Unfortunately, little is still known about the susceptibility factors that govern the behavioral outcomes of cannabis in patients affected by anxiety-spectrum disorders.
Indeed, several components have been shown to play a role in this link, including genetic background, age, gender, environmental stress and concurrent use of other drugs; a detailed analysis of these determinants is outside the scope of the present work, but the interested reader should refer to [ ].
Aside from the influence of vulnerability factors, the available evidence indicates that cannabis, THC and other CB 1 receptor agonists exercise a bidirectional influence on anxiety responses as a function of the dosage. The majority of users report that consumption of modest amounts of cannabis and CB 1 receptor agonists results in euphoria, relaxation, heightened perception, sociability and creativity, moderate to high doses have been reported to elicit phobia, agitation, panic, dysphoria, psychotic manifestations and cognitive impairments [ - , , - ].
In line with these premises, early studies showed a robust anxiolytic efficacy of low-dose nabilone in comparison with placebo [ , ]. The biphasic effects of cannabinoids on anxiety-related responses have been extensively documented in rodents. The bidirectional action of CB 1 receptors on anxiety responses may be related to the modulatory role of these targets on GABA and glutamate release across amygdala and other forebrain areas [ 41 , , ]. As these two major neurotransmitters affect anxiety in an opposite fashion, different doses of cannabinoids and synthetic CB 1 receptor agonists may indeed produce highly divergent effects, in relation to their ability to affect the homeostasis and the balance of GABA and glutamate for a review on these issues, see [ ].
Furthermore, CB 1 receptors have been shown to play critical roles in the regulation of most neurochemical substrates of anxiety, including the neurotransmitters serotonin, norepinephrine and acetylcholine, as well as stress hormones, colecystokynin and opioid peptides [ 50 , ].
In line with this concept, the infusion in the periaqueductal grey of arachidonylchloroethylamide ACEA , an anandamide synthetic analog with high CB 1 receptor selectivity, elicited anxiolytic-like effects in rats in an elevated plus maze, with a bell-shaped dose-response curve [ ], the highest doses being associated to no significant behavioral change. Novel categories of compounds have been patented for potential efficacy as selective CB 1 receptor modulators, including sulfonyl-benzamides [ ] and tetrasubstituted imidazole derivatives [ ].
To the best of our knowledge, however, no findings on the action of these compounds in anxiety regulation have been reported to date. The majority of preclinical studies found that these compounds are anxiogenic at high doses [ , , , ] and ineffective at low doses [ , ].
The anxiogenic properties of CB 1 antagonists, were unequivocally confirmed by clinical data on the psychiatric side effects of rimonabant. The significant increase in anxiety, depression and suicidality in patients under treatment with rimonabant [ - ], in particular, led to the withdrawal of the drug from the European market in October, As a consequence, several pharmaceutical companies announced the interruption of their clinical research on CB 1 receptor antagonists, including taranabant from Merck and otenabant from Pfizer , both in Phase 3 of development.
Some of the anxiogenic properties of rimonabant and analogs have been speculated to be due to their activity as inverse agonists; as a result, the therapeutic use of newly-developed neutral CB 1 antagonists has been proposed, with the hypothesis that these compounds would not elicit the untoward psychological effects observed with rimonabant and its analogs [ , ]; this idea is supported by recent findings, showing that unlike CB 1 receptor inverse agonists, the neutral antagonists of this targets fail to facilitate the acquisition or consolidation of fear [ ].
Few studies have actually evaluated the role of CB 2 receptor in anxiety and stress response. Some of these investigations indicated that the suppression of CB 2 receptor in the brain, through intracerebroventricular injection of antisense nucleotide sequences, elicited anxiolytic effects in rodents [ ]. In contrast, Garcia-Gutierrez and Manzanares [ ] recently described that the overexpression of CB 2 receptors reduced anxiogenic-related behaviors in the light-dark box and elevated plus maze.
These premises point to the possibility that CB 2 receptor ligands may also play a role in the modulation of anxiety disorders. This hypothesis, however, awaits further examination with proper pharmacological tools.
Several lines of preclinical work have shown that CBD reduces the effects of THC on several behavioral functions [ - ]. In line with these data, CBD has been found to reduce the anxiety and improve the sensation of well being induced by an acute, high THC dose in healthy volunteers [ ].
In contrast with these data, a number of studies have shown that CBD pretreatment potentiated the behavioral effects induced by THC [ - ]. These actions may signify the ability of CBD to inhibit cytochrome Pmediated drug metabolism [ , ], which may increase THC blood and brain concentrations [ , ].
Of note, the anxiolytic action of CBD also appears to be bidirectional, as only low to moderate doses, but not high doses, have been associated with exert anxiolytic effects [ , ]. The anxiolytic action of CBD do not appear to be mediated by benzodiazepine receptors [ ], but rather by 5-HT 1A serotonin receptors in the bed nucleus of the stria terminalis [ ], a critical component of the amygdaloid complex involved in the regulation of stress response.
Accordingly, CBD has been shown to reduce amygdalar responses to fearful stimuli [ ]; this mechanism may be essential for the anxiolytic effects of this compound in social phobia [ ]. Furthermore, CBD has been shown to elicit antipanic effects through the activation of 5-HT 1A receptors in the dorsal periaqueductal gray, a critical area for the modulation of emotional reactivity to stress [ , ].
The systemic administration of the endocannabinoid transport blocker AM Fig. The same compound was shown to attenuate marble burying a paradigm for compulsivity testing in mice, suggesting that this compound may have some potential efficacy for OCD [ ]. Interestingly, the anxiolytic effects of AM were shown to be contributed by both CB 1 and 5-HT 1A receptors [ , ], in a fashion similar to the potent CB 1 receptor agonist CP 55, [ ].
Additionally, AM has been suggested to act as a FAAH inhibitor [ ], although evidence in this respect is controversial [ 72 ]. Chemical structures of endocannabinoid degradation inactivators. Although the possibility of targeting the endocannabinoid carrier for the development of anxiolytic compounds is appealing and has been targeted by a patent proposing these compounds as a pharmacological support for psychotherapy [ ], the elusive molecular identity of the transporter itself has greatly limited the studies.
Furthermore, preliminary data indicate that AM elicits reward in animals and is self-administered by squirrel monkeys [ , ], raising the possibility that endocannabinoid transport blockers may be addictive. In addition to its anxiolytic-like properties, URB was found to exert also antidepressant-like effects in several animal models with high face and predictive validity, such as the forced swim, tail suspension and chronic mild stress paradigms [ 89 , , , ].
The anxiolytic action of FAAH inhibitors has been suggested to depend on the enhancement of anandamide in the dorsolateral periaqueductal gray [ ]; interestingly, however, only low doses of URB in the prefrontal cortex were found to elicit anxiolytic-like effects, through CB 1 receptor activation.
However, higher doses ceased to elicit anxiolysis, in view of their interaction with TPRV1 vanilloid receptors [ ]. Furthermore, the anxiolytic and antidepressant actions of FAAH inhibitors were observed only under conditions of high environmental aversiveness, but not under normal conditions [ , , ]. Importantly, the psychotropic effects of FAAH inhibitors are partially distinct from those associated with cannabinoids, in that they appear to fail to reproduce the hedonic and interoceptive states produced by CB receptor agonists [ 89 ] and to induce self-administration in squirrel monkeys [ ].
Taken together, these data suggest that FAAH inhibitors may be promising tools in the therapy of anxiety and mood disorders with a safer profile than cannabinoid direct agonists. This idea has been recently endorsed by several authors in recent articles and patents, featuring novel categories of highly selective and potent FAAH inhibitors [ - ] [ ]. However, it should be noted that recent data have recently shown that URB induce a number of side effects in rats, including social withdrawal, working memory deficits [ ] and impairments in auditory discrimination and reversal of olfactory discrimination [ ].
The role of 2-AG in emotional regulation has been difficult to ascertain until the recent development of highly selective monoacylglycerol lipase MAGL inhibitors [ 35 , ]. Several lines of evidence have suggested that 2-AG plays a pivotal role in the pathophysiology of anxiety and defensive behaviors. Recent evidence has shown that this compound exerts anxiolytic-like effects in the elevated plus maze and in marble buyring, at doses that do not affect locomotor activity [ 93 , , ].
Similarly to the effects described for FAAH inhibitors see above , the anxiolytic effects of this compound were observed in highly aversive or anxiogenic contextual settings [ ]. The neurobiological role of 2-AG in anxiety is still poorly understood, although several studies have shown that environmental stressors alter its biosynthesis and degradation in key brain structures controlling emotional regulation, including periaqueductal grey, amygdala and hippocampus [ , ].
Interestingly, recent evidence has shown that the anxiolytic properties of JZL appear to be mediated by CB 2 , rather than CB 1 receptors [ 93 ], pointing to a potential implication of this receptor in the role of 2-AG in anxiety regulation.
In light of the limitations of our current pharmacological armamentarium for anxiety disorders, the ability of cannabinoids to modulate emotional responses is extremely attractive for the development of novel anxiolytic agents [ ]. At the same time, great concern arises from the protean role of cannabinoids on the regulation of these responses, as well as their misuse liability and other side effects. The identification of operational strategies for the employment of cannabinoids in the therapy of anxiety disorders is therefore a fundamental goal in psychiatry research.
As outlined above, clinical evidence strongly suggests that acute administration of low doses of CB 1 receptor agonists results in anxiolytic effects, while excessive activation of these targets elicits opposite outcomes, following a reverse U-shaped dose-response pattern. This concept indicates a potential evolution in the search for direct CB agonists, in sharp contrast with the previous trend aimed at the identification of high-affinity CB receptor activators.
However, recent preliminary clinical studies have shown that this formulation did not significantly reduce anxiety in fact, it was reported to induce a mild, yet not significant increase of this symptom [ , ], and that CBD did not appear to elicit a significant opposition to the effect of dronabinol [ ], plausibly indicating that a higher concentration of this ingredient or lower relative amount of THC may be necessary to elicit anxiolytic effects.
A third, highly promising avenue for the development of cannabinoid-based anxiolytic therapies may be afforded by FAAH inhibitors. Unlike endocannabinoid transport blockers and direct CB receptor agonists, these compounds exhibit a number of highly desirable properties for anxiolytic agents: The neurobiological bases of this phenomenon are not completely understood, and may be related to the involvement of other FAAH substrates, such as OEA or PEA; however, recent investigations suggest that the lack of 2-AG enhancement ensuing FAAH inactivation may contribute to the lack of reinforcing properties of URB [ ], potentially suggesting a different role of anandamide and 2-AG in the modulation of reward; this idea is actually consistent with the recent finding that 2-AG is induces self-administration in monkeys [ ].
A key problem concerning the potential application of cannabinoid-related agents and cannabinoids is the relatively little information about their long-term effects following chronic administration. Indeed, the subjective effects of cannabis have been shown to be typically different in chronic users as compared to occasional marijuana smokers [ , ]. Prolonged consumption of cannabis has been shown to induce affective sequelae, including alexithymia and avolition [ , - ].
Interestingly, tolerance has been shown to the effects of THC [ , ], while no information is available on endocannabinoid-related agents. Long-term administration of cannabinoids has been shown to result in a number of neuroplastic adaptive processes, including CB receptor down-regulation [ , ].
Some of these phenomena may indeed be critical in shaping the different emotional responsiveness to cannabis throughout life and reflect a potential pathophysiological loop which may compound the severity of pre-existing anxiety and affective disorders.
Finally, another important step for the employment of cannabinoid-based anxiolytic therapies will be the analysis of the vulnerability factors implicated in the differential responses and long-term sequelae induced by cannabis consumption. For example, numerous meta-analyses and longitudinal studies have established that cannabis consumption in adolescence is conducive to an increased risk for psychotic disorders [ - ].
This association is particularly significant in the presence of other genetic factors, such as the Val Met allelic variant of the gene encoding Catechol-O-methyltransferase COMT [ , ], one of the main enzymes for the degradation of the neurotransmitter dopamine.
Interestingly, it has been shown that the synergistic effect of COMT haplotype and cannabis in adolescence is more robust in conjunction with predisposing environmental variables, such as the exposure to urbanicity and psychosocial stress [ ].
Another gene that may modulate the behavioral responsiveness to cannabinoids is Nrg1 , which encodes for the synaptic protein neuregulin 1. Indeed, the heterozygous deletion of this gene ablates the development of tolerance to the anxiogenic effects of CB receptor agonists [ , ].
These findings suggest that the employment of a pharmacogenetic approach may be a critical screening instrument to identify which patients may be treated with cannabis for medical purposes without risks of neuropsychiatric side effects.
Notably, the role of genes in the mental sequelae of cannabis may also be contributed by epigenetic factors, in consideration of the recent finding that THC induces expression of histone deacetylase 3 [ ]. While studies on the biological determinants of different responses to cannabis are still at their preliminary stages, advances in this area may be essential to allow a personalized approach for the employment of cannabinoid-based therapies in anxiety and mood disorders.
National Center for Biotechnology Information , U. Author manuscript; available in PMC Jun Simone Tambaro and Marco Bortolato. Author information Copyright and License information Disclaimer. See other articles in PMC that cite the published article. Abstract Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation.
According to the current classification of anxiety disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders DSM-IV [ 2 ], the main diagnostic entities in this category are: Table 1 Current pharmacological strategies for the treatment of anxiety disorders. Generalized anxiety disorder Benzodiazepines. Panic attack High-potency benzodiazepines. Post-traumatic stress disorder Selective serotonin reuptake inhibitors.
Obsessive-compulsive disorder Tricyclic antidepressants. Open in a separate window. Table 2 Paradigms for testing of anxiety-like behaviors in rodents.
Unconditioned anxiety Tests for social anxiety Maternal separation-induced ultrasonic vocalizations for pups. Tests based on antipredator defensive behavior Mouse defense test battery. Other tests Novelty-induced feeding suppression. Conditioned anxiety Tests on conditional fear Fear- conditioned freezing. Operant conflict test Geiller-Seifter test conditioned suppression of eating.
Chemical structures of the major phytocannabinoids. Synthetic cannabinoids In addition to phytocannabinoids, several classes of synthetic CB receptor agonists have been developed; among these families, the best characterized are the synthetic analogs of THC - such as the biciclic compounds CP 47,, CP 55,, CP 55, and the benxopyrans HU and nabilone Fig.
Chemical structures of the major endocannabinoids. Endocannabinoids Both anandamide and 2-AG are derivatives of arachidonic acid, an unsaturated C20 fatty acid with 4 double bonds, which also serves as the precursor for synthesis of other eicosanoids, including prostaglandins and leukotriens.
CB 2 receptor ligands Few studies have actually evaluated the role of CB 2 receptor in anxiety and stress response. Endocannabinoid transport blockers The systemic administration of the endocannabinoid transport blocker AM Fig. MAGL inhibitors The role of 2-AG in emotional regulation has been difficult to ascertain until the recent development of highly selective monoacylglycerol lipase MAGL inhibitors [ 35 , ]. Establishing non-inferiority in treatment trials in psychiatry: Sugiura T, Waku K.
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Can Using Medical Marijuana Increase Anxiety and Depression?
However, the emergence of cannabis-induced cause of symptom onset without mediation of anxiety symptoms. Cannabis-induced anxiety affects many marijuana consumers. With legal weed becoming more common, more people are consuming too. With new marijuana laws and weed legalization, it's becoming more and more common to hear about people getting struck with anxiety and.