Herbal Cannabis and Depression: A Review of Findings Published over the Last Three Years

PHARMACEUTICALS 17 : 6, 2024, Haller József

Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.

The effects of expected and unexpected stress on inappropriate aggression in simulated police interventions

HELIYON 9 : 7, 2023, Farkas István, Végh József, Ivaskevics Krisztián, Szabó Erika Malét, Haller József

Here we performed a before-after ABA-design study in police cadets (N = 82) to compare the effects of unexpected (event-triggered) and expected (anticipatory) stressors on aggression. On the first day of the study, participants filled in the Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale (BIS) and were fitted with heart rate (HR) monitors, which remained attached till the end of the study. On day 2, they were instructed to perform a police intervention in a realistic training environment. The intervention was preceded either by a warning or by a reassuring audio recording that forecasted violent or routine interventions, respectively. Both groups encountered hostile suspects at the intervention site, the behavior of which, however, did not justify the use of force e.g., aggression. The warning resulted in a gradually developing anticipatory stress as shown by HRs. Cadets exposed to the reassuring audio recording showed minimal anticipatory stress but responded to the hostile suspects by an abrupt increase in HRs, which was missing in the warned group. The magnitude of HR responses was similar in the two groups, only their temporal evolution differed. Although aggression showed some associations with BPAQ and BIS scores, the main predictors of behavior were HR changes according to a Multiple Regression analysis. The gradually developing anticipatory stress was associated with low, whereas the abrupt increase in HRs was associated with high aggression. Our findings suggest that the anticipation of a stressful event improves behavioral control whereas an unexpected stress strongly promotes aggression.

Anxiety Modulation by Cannabinoids —The Role of Stress Responses and Coping

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 : 21, 2023, Haller József

Endocannabinoids were implicated in a variety of pathological conditions including anxiety and are considered promising new targets for anxiolytic drug development. The optimism concerning the potentials of this system for anxiolysis is probably justified. However, the complexity of the mechanisms affected by endocannabinoids, and discrepant findings obtained with various experimental approaches makes the interpretation of research results difficult. Here, we review the anxiety-related effects of the three main interventions used to study the endocannabinoid system: pharmacological agents active at endocannabinoid-binding sites present on both the cell membrane and in the cytoplasm, genetic manipulations targeting cannabinoid receptors, and function-enhancers represented by inhibitors of endocannabinoid degradation and transport. Binding-site ligands provide inconsistent findings probably because they activate a multitude of mechanisms concomitantly. More robust findings were obtained with genetic manipulations and particularly with function enhancers, which heighten ongoing endocannabinoid activation rather than affecting all mechanisms indiscriminately. The enhancement of ongoing activity appears to ameliorate stress-induced anxiety without consistent effects on anxiety in general. Limited evidence suggests that this effect is achieved by promoting active coping styles in critical situations. These findings suggest that the functional enhancement of endocannabinoid signaling is a promising drug development target for stress-related anxiety disorders.

Drug regulations and trafficking: synthetic cannabinoids and cathinones in Hungary

FORENSIC SCIENCE INTERNATIONAL 349 Paper: 111778, 2023,  Haller József, Rompos Éva, Szabó Írisz, Humli Viktória, Christián László 

In principle, new psychoactive substances (NPSs) are produced to circumvent drug regulations. However, the mixed success of regulatory efforts suggests that the dynamics of marketing is incompletely understood. To address this issue, we conducted a comprehensive study on the marketing of all synthetic cannabinoids and cathinones present in Hungary over ten years. Market evaluation was based on drug seizure data and chemical analyses provided by the Hungarian Institute for Forensic Sciences. Over ten years, 18 synthetic cannabinoids and 11 cathinones were identified. Total seizure counts were 22,906 and 10,273, respectively. When new synthetic cannabinoids emerged, seizures increased exponentially, but rapidly declined after their banning. In parallel, new synthetic cannabinoids emerged on the market. The systematic monitoring of local legislation allowed large sales between market introduction and legal control. Cathinones were also marketed in successive waves, but trading intensity was not associated with local regulations. Sales remained low throughout, likely because the risks involved by the temporal mismatch between marketing and legal control. One can hypothesize that marketing was driven by general trends in EU regulations or by measures taken by large countries. Our findings imply the existence of two different strategies for NPS marketing. The choice between the two may depend on multiple factors from the availability of skills required by rapid marketing adjustments to cost/benefit evaluations for various market segments. Studying NPS market strategies in neighboring and distant EU countries may help analyzing and predicting market events.

Aggression, Aggression-Related Psychopathologies and Their Models

FRONTIERS IN BEHAVIORAL NEUROSCIENCE 16 pp. 1-12, 2022, Haller József

Neural mechanisms of aggression and violence are often studied in the laboratory by means of animal models. A multitude of such models were developed over the last decades, which, however, were rarely if ever compared systematically from a psychopathological perspective. By overviewing the main models, I show here that the classical ones exploited the natural tendency of animals to defend their territory, to fight for social rank, to defend themselves from imminent dangers and to defend their pups. All these forms of aggression are functional and adaptive; consequently, not necessarily appropriate for modeling non-natural states, e.g., aggression-related psychopathologies. A number of more psychopathology-oriented models were also developed over the last two decades, which were based on the etiological factors of aggression-related mental disorders. When animals were exposed to such factors, their aggressiveness suffered durable changes, which were deviant in the meaning that they broke the evolutionarily conserved rules that minimize the dangers associated with aggression. Changes in aggression were associated with a series of dysfunctions that affected other domains of functioning, like with aggression-related disorders where aggression is just one of the symptoms. The comparative overview of such models suggests that while the approach still suffers from a series of deficits, they hold the important potential of extending our knowledge on aggression control over the pathological domain of this behavior.