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The endocannabinoid system is known to be involved in mechanisms relevant to PTSD aetiology and maintenance, though this understanding is mostly based on animal models of the disorder. Here we review how human paradigms can successfully translate animal findings to human subjects, with the view that substantially increased insight into the effect of endocannabinoid signalling on stress responding, emotional and intrusive memories, and fear extinction can be gained using modern paradigms and methods for assessing the state of the endocannabinoid system in PTSD.

Neurobiological models indicate that acute stress facilitates bottom-up stimulus processing while impairing top-down executive control. To test this hypothesis, the present study investigated the effects of acute stress on behavioural and electrophysiological measures of human attentional networks, and behavioural measures of working memory. Forty-five female participants (Mage = 22.1, SD = 2.4) performed the Attention Network Test (ANT) and the n-back task before and after the Maastricht Acute Stress Test (MAST; n = 23) or a non-stressful MAST-placebo (n = 22). Subjective distress ratings and salivary cortisol concentrations revealed a successful stress induction. Increased salivary cortisol at baseline was associated with slower reaction times across both tasks, suggesting a general detrimental effect of cortisol on cognitive functioning. Despite these findings, however, the hypothesised effects of the acute stress manipulation were not found for either task. Supplementary analyses indicated that these results were unrelated to the magnitude or duration of the stress response. Our results therefore suggest the standard version of the ANT may be insensitive to the effects of acute stress, and that higher cognitive loads may be necessary to observe stress effects on the n-back task.

Understanding the role of endogenous cannabinoids (endocannabinoids) in disease is of increasing importance. However, tools to investigate endocannabinoid levels in humans are limited. In the current study, we report a simplified sample preparation method for quantifying endocannabinoids and steroid hormones in hair using liquid-liquid extraction combined with ultra performance liquid chromatography coupled to tandem mass spectrometry. The fully validated method is at least R2 = 0.99 linear between 5 and 1,000 pg/mg for each analyte and the detection limits are at or below 0.50 pg/mg for cortisol, progesterone, oleoylethanolamide, and arachidonoyl ethanolamide, and 2.65 pg/mg for 2-arachidonoyl glycerol. Sequential extraction of hair samples revealed that multiple extractions may be required for quantitative recovery of steroids. However endogenous cannabinoids were efficiently recovered using a single sample extraction. The method was applied to a psychosocial stress study where participants provided samples of both hair and saliva. Endogenous hair arachidonoyl ethanolamide levels were negatively associated with resting, but not stressed, salivary cortisol levels in healthy participants. This simplified method enables the detailed study of hormonal and endocannabinoids in human hair with high sensitivity.

The endogenous cannabinoid (eCB) system has been shown in animal models to regulate the initiation and termination of central nervous responses to stress. In human studies, the role of peripherally measured eCBs is much less clear and the effect in salivary eCBs has not been studied. In this study, we use a novel method to quantify cortisol and eCBs arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) in human saliva, as well as in plasma samples. Forty-five females and 32 males completed a mixed physiological/psychosocial stress-induction study where saliva, and blood samples in males, were collected at baseline, immediately following, 30-minutes following, and 45-minutes following stress induction. Cortisol significantly increased after stress, but there were sex differences in the cortisol response to stress, with females having higher cortisol after stress compared to males. There was a significant increase in salivary levels of 2-AG immediately following stress induction, but no effect of AEA. Salivary AEA was higher in males compared to females. Surprisingly, there was no effect of stress on plasma AEA or 2-AG levels in the male cohort, though small effect sizes for 2-AG were observed, which is consistent with most other human literature. This study is the first to show that the eCB system is active in human saliva and is responsive to acute stress, possibly as part of the sympathetic nervous system response.

Brain-derived neurotropic factor (BDNF) is a potent regulator of memory processes and is believed to influence the consolidation of fear extinction memories. No previous human study has tested the effect of unstimulated BDNF on fear extinction recall, and no study has tested the association between plasma BDNF levels and psychophysiological responding during an extinction paradigm. We tested the association between fear responses during a 2-day differential conditioning, extinction and extinction recall paradigm and Val66Met genotype in a group of healthy participants (N = 191). There were no group differences during habituation or acquisition. Met allele carriers compared to Val homozygotes displayed higher responses to the CS + compared to the CS- during extinction learning and had higher responding to both the CS+ and CS- during extinction recall. Plasma levels of BDNF protein that were collected in a sub-sample of the group (n = 56) moderated the effect of Met allele presence, such that lower BDNF level was associated with higher skin conductance response in the Met but not Val group to the CS+ during extinction learning and to both the CS+ and CS- during extinction recall. The current results extend previous observations of a Val66Met effect during fear extinction learning to extinction recall and show for the first time that these effects are moderated by plasma BDNF level.

There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder. Based on current evidence, we outline an early, preliminary model that links re-experiencing and negative cognitions and mood in PTSD by invoking the interaction between endocannabinoid and dopaminergic signalling in the brain. These interactions between PTSD, dopamine and endocannabinoids may have implications for future therapies for treatment-resistant and comorbid PTSD patients.

Background: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. Methods: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. Results: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSD participants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSD participants. Subanalysis of healthy participants (n = 57) showed the FAAH rs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAH rs324420 were associated with better extinction learning. Conclusions: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAH rs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.

Endogenous cannabinoids are an increasingly intriguing target for biological research, given the changing legal status of medicinal cannabinoid-based products throughout the world. However, studying the endogenous cannabinoid system is a relatively new field, with few research teams attempting to develop quantitative methods for these important modulatory analytes in human matrices, other than blood. Here we develop and validate simultaneous methods for quantifying arachidonoyl-ethanolamide, 2-arachidonoyl glycerol, oleoylethanolamide, cortisol and progesterone in human plasma and saliva using liquid–liquid extraction combined with ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The method was fully validated over the linear concentration range 1–20 ng/mL for each analyte in plasma (R2 = 0.98–0.99) and saliva (R2 = 0.99). We find that salivary endogenous cannabinoids and cortisol are acutely responsive to exercise, suggesting that targeting the saliva system may present a convenient way for future research of endogenous cannabinoids. This finding also encourages a broader understanding of the endogenous cannabinoid system during stress responses, and our method may consequently lead to a better understanding of the role of endogenous cannabinoids in peripheral tissues.

There is now significant literature suggesting that increasing brain-derived neurotropic factor (BDNF) signalling may improve memory-related disorders such as Alzheimer’s disease. However, the effects of BDNF on short-term and working memory are not clear and existing evidence is inconsistent. Here we measured plasma BDNF and salivary cortisol levels, as well as working memory, on an N-Back task before and after mixed psychosocial/physiological stress induction in healthy males (N = 29). Stress induction was associated with higher circulating cortisol, but not BDNF levels. Higher cortisol and BDNF levels were significantly associated with poorer accuracy before and after stress induction. There was also a significant interaction, such that higher BDNF was associated with a buffering effect on the negative association between high cortisol and working memory. Future studies should replicate this data in larger samples, with emphasis on cortisol/BDNF interactions in determining working memory performance.

Cannabinoids are a promising method for pharmacological treatment of post-traumatic stress disorder (PTSD). Despite considerable research devoted to the effect of cannabinoid modulation on PTSD symptomology, there is not a currently agreed way by which the cannabinoid system should be targeted in humans. In this review, we present an overview of recent research identifying neurological pathways by which different cannabinoid-based treatments may exert their effects on PTSD symptomology. We evaluate the strengths and weaknesses of each of these different approaches, including recent challenges presented to favourable options such as fatty acid amide hydrolase (FAAH) inhibitors. This article makes the strengths and challenges of different potential cannabinoid treatments accessible to psychological researchers interested in cannabinoid therapeutics and aims to aid selection of appropriate tools for future clinical trials.

The endocannabinoid system is an increasingly recognised pharmacological target for treating stress and anxiety disorders, including post-traumatic stress disorder (PTSD). Recent preclinical developments have implicated the endocannabinoid system in stress responses, emotional memories and fear extinction, all critical to PTSD aetiology. However, preclinical research in endocannabinoid biology has neglected the influential role of sex hormone differences on PTSD symptomology, which is particularly important given that PTSD is twice as common in women as in men. In this review, we compile and consider the evidence that the endocannabinoid system is influenced by ovarian hormones, with application to stress disorders such as PTSD. It is clear that therapeutic modulation of the endocannabinoid system needs to be approached with awareness of ovarian hormonal influences, and knowledge of these influences may enhance treatment outcomes for female PTSD populations.

Aims: Long-term heavy use of cannabis and alcohol are known to be associated with memory impairments. In this study, we used event-related potentials to examine verbal learning and memory processing in a commonly used behavioral task. Method: We conducted two studies: first, a small pilot study of adolescent males, comprising 13 Drug-Naive Controls (DNC), 12 heavy drinkers (HD) and 8 cannabis users (CU). Second, a larger study of young adults, comprising 45 DNC (20 female), 39 HD (16 female), and 20 CU (9 female). In both studies, participants completed a modified verbal learning task (the Rey Auditory Verbal Learning Test, RAVLT) while brain electrical activity was recorded. ERPs were calculated for words which were subsequently remembered vs. those which were not remembered, and for presentations of learnt words, previously seen words, and new words in a subsequent recognition test. Pre-planned principal components analyses (PCA) were used to quantify the ERP components in these recall and recognition phases separately for each study. Results: Memory performance overall was slightly lower than published norms using the standardized RAVLT delivery, but was generally similar and showed the expected changes over trials. Few differences in performance were observed between groups; a notable exception was markedly poorer delayed recall in HD relative to DNC (Study 2). PCA identified components expected from prior research using other memory tasks. At encoding, there were no between-group differences in the usual P2 recall effect (larger for recalled than not-recalled words). However, alcohol-related differences were observed in a larger P540 (indexing recollection) in HD than DNC, and cannabis-related differences were observed in a smaller N340 (indexing familiarity) and a lack of previously seen > new words effect for P540 in Study 2. Conclusions: This study is the first examination of ERPs in the RAVLT in healthy control participants, as well as substance-using indiv

Background: The past five years has seen a proliferation in marketplaces operating on the ‘dark net’ selling licit and illicit substances. While monitoring systems have investigated the specific substances for sale on these marketplaces, less is known about consumer motivations for accessing these marketplaces and factors associated with their use. Methods: An Australian national sample (n = 800) recruited on the basis of regular psychostimulant use was recruited and asked about purchasing substances from dark net marketplaces and the reasons for doing so. Respondents who had purchased any drug from a dark net marketplace in the preceding year were compared to those who had not in terms of demographic information and factors including drug use, criminal activity, and sexual and mental health. Results: Nine percent (n = 68) of the sample had purchased from dark net markets in the past year. MDMA, LSD and cannabis were the three most commonly purchased substances, and the main benefits cited for purchasing online were the better quality and lower cost of drugs available. Controlling for other factors, participants who purchased from dark net marketplaces in the past year tended to be younger, more likely to be involved in recent property crime and to have used more classes of drugs in the preceding six months, specifically psychedelics and ‘new psychoactive drugs’. Conclusions: Though a small minority of participants reported having purchased drugs online in the preceding six months, these appeared to be a more ‘entrenched’ group of consumers, with more diverse substance use and rates of criminal activity. For consumers in the current sample reporting recent dark net usage, country borders are now less of a significant barrier to purchase and there is a wider range of substances available than ever before.

The purpose of this Area Handbook for India is to describe briefly and in general terms the political, economic and social basis of Indian society, to outline its domestic and foreign policies and to evaluate its strengths and weaknesses. The present study represents a thorough revision of the Human Relations Area Files Area Handbook for India, which was issued in 1958, to consider the fundamental changes which have taken place and to utilize the many source materials which have become available since the earlier study was published. It supersedes the Interim Revision to the Area Handbook for India, published in March 1963 to fill the immediate need for an updated edition of the original Handbook pending the completion of the full revision. (Author), Also available from U.S. Government Printing Office, Washington 25, D. C., Price $2.50.