Lysergic acid diethylamide as an analgesic agent in patients with terminal illnesses
Das, S., & Maiti, T. (2020). Lysergic acid diethylamide as an analgesic agent in patients with terminal illnesses., 10.2217/pmt-2019-0043
Link to full text
Psychiatry & Medicine
4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels
Abstract
Rationale: A high number of synthetic dissociative drugs continue to be available through online stores, leading to their misuse. Recent inclusions in this category are 4-MeO-PCP and 3-MeO-PCMo, analogs of phencyclidine. Although the dissociative effects of these drugs and their recreational use have been reported, no studies have investigated their abuse potential.
Objectives: To examine their rewarding and reinforcing effects and explore the mechanistic correlations.
Methods: We used conditioned place preference (CPP), self-administration, and locomotor sensitization tests to assess the rewarding and reinforcing effects of the drugs. We explored their mechanism of action by pretreating dopamine receptor (DR) D1 antagonist SCH23390 and DRD2 antagonist haloperidol during CPP test and investigated the effects of 4-MeO-PCP and 3-MeO-PCMo on dopamine-related proteins in the ventral tegmental area and nucleus accumbens. We also measured the levels of dopamine, phosphorylated cyclic-AMP response element-binding (p-CREB) protein, deltaFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens. Additionally, we examined the effects of both drugs on brain wave activity using electroencephalography.
Results: While both 4-MeO-PCP and 3-MeO-PCMo induced CPP and self-administration, only 4-MeO-PCP elicited locomotor sensitization. SCH23390 and haloperidol inhibited the acquisition of drug CPP. 4-MeO-PCP and 3-MeO-PCMo altered the levels of tyrosine hydroxylase, DRD1, DRD2, and dopamine, as well as that of p-CREB, deltaFosB, and BDNF. All drugs increased the delta and gamma wave activity, whereas pretreatment with SCH23390 and haloperidol inhibited it.
Conclusion: Our results indicate that 4-MeO-PCP and 3-MeO-PCMo induce rewarding and reinforcing effects that are probably mediated by the mesolimbic dopamine system, suggesting an abuse liability in humans.
Abiero, A., Botanas, C. J., Custodio, R. J., Sayson, L. V., Kim, M., Lee, H. J., … & Cheong, J. H. (2020). 4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels. Psychopharmacology, 237(3), 757-772; 10.1007/s00213-019-05412-y
Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment
Abstract
Rationale
5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce.
Objectives
The first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1β), as well as the acute psychedelic experience.
Methods
Assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA).
Results
5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment.
Conclusion
Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,N-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.
Uthaug, M. V., Lancelotta, R., Szabo, A., Davis, A. K., Riba, J., & Ramaekers, J. G. (2019). Prospective examination of synthetic 5-methoxy-N, N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology, 1-13., 10.1007/s00213-019-05414-w
Link to full text
The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression
Abstract
Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine’s treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine’s proposed ability to block trauma-associated behavioral sensitization.
O’Brien, B., Lijffijt, M., Wells, A., Swann, A. C., & Mathew, S. J. (2019). The impact of childhood maltreatment on intravenous ketamine outcomes for adult patients with treatment-resistant depression. Pharmaceuticals, 12(3), 133., 10.3390/ph12030133
Link to full text
Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders
Abstract
Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.
Sartori, S. B., & Singewald, N. (2019). Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacology & therapeutics, 107402., 10.1016/j.pharmthera.2019.107402
Link to full text
N,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model
Abstract
BACKGROUND:
Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure.
OBJECTIVE:
To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats.
METHOD:
In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically.
RESULTS:
Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals.
CONCLUSION:
Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.
Nemes, B., Pető, K., Németh, N., Mester, A., Magyar, Z., Ghanem, S., … & Bidiga, L. (2019, May). N, N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model. In Transplantation proceedings (Vol. 51, No. 4, pp. 1268-1275). Elsevier. 10.1016/j.transproceed.2019.04.005
Link to full text
Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action
Abstract
Salvia divinorum is a herbal plant native to the southwest region of Mexico. Traditional preparations of this plant have been used in illness treatments that converge with inflammatory conditions and pain. Currently, S. divinorum extracts have become popular in several countries as a recreational drug due to its hallucinogenic effects. Its main active component is a diterpene named salvinorin A (SA), a potent naturally occurring hallucinogen with a great affinity to the κ opioid receptors and with allosteric modulation of cannabinoid type 1 receptors. Recent biochemical research has revealed the mechanism of action of the anti-inflammatory and analgesic effect of SA at the cellular and molecular level. Nevertheless, because of their short-lasting and hallucinogenic effect, the research has focused on discovering a new analogue of SA that is able to induce analgesia and reduce inflammation with a long-lasting effect but without the hallucinatory component. In this review, we explore the role of S. divinorum, SA and its analogues. We focus mainly on their analgesic and anti-inflammatory roles but also mention their psychoactive properties.
Coffeen, U., & Pellicer, F. (2019). Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of pain research, 12, 1069., 10.2147/JPR.S188619
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety
Abstract
BACKGROUND:
A recent epidemiological study suggested that 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials.
OBJECTIVES:
We examined self-reported improvement in depression and anxiety among people who use 5-MeO-DMT in a group setting with structured procedures guiding dose and administration of 5-MeO-DMT. Such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. Next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions.
METHODS:
Respondents (n = 362; Mage = 47.7; Male = 55%; White/Caucasian = 84%) completed an anonymous web-based survey.
RESULTS:
Of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression = 80%; anxiety = 79%) following 5-MeO-DMT use, and fewer reported they were unchanged (depression = 17%; anxiety = 19%) or worsened (depression = 3%; anxiety = 2%). Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-MeO-DMT experience.
CONCLUSIONS:
Future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety.
Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2018). 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American journal of drug and alcohol abuse, 1-9., 10.1080/00952990.2018.1545024
Link to full text
Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder
Abstract
OBJECTIVE::
Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder.
METHODS::
Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday-Wednesday-Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively.
RESULTS::
After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, p<0.001), and this decrease was maintained for the duration of the infusion period. The response to ketamine treatment was positively associated with no history of psychiatric hospitalization (odds ratio=3.56, p=0.009). Suicidal ideation rapidly decreased across the entire study sample, even among the nonresponder group. No significant differences were found regarding Brief Psychiatric Rating Scale and Clinician Administered Dissociative States Scale scores from the first infusion at baseline to four hours post-infusion.
CONCLUSION::
Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.
Zheng, W., Zhou, Y. L., Liu, W. J., Wang, C. Y., Zhan, Y. N., Li, H. Q., … & Ning, Y. P. (2019). Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder. Journal of Psychopharmacology, 0269881119827811., 10.1177/0269881119827811
Link to full text
Long-lasting analgesic effect of the psychedelic drug changa: A case report
Abstract
Background and aims
Pain is the most prevalent symptom of a health condition, and it is inappropriately treated in many cases. Here, we present a case report in which we observe a long-lasting analgesic effect produced by changa, a psychedelic drug that contains the psychoactive N,N-dimethyltryptamine and ground seeds of Peganum harmala, which are rich in β-carbolines.
Methods
We describe the case and offer a brief review of supportive findings.
Results
A long-lasting analgesic effect after the use of changa was reported. Possible analgesic mechanisms are discussed. We suggest that both pharmacological and non-pharmacological factors could be involved.
Conclusion
These findings offer preliminary evidence of the analgesic effect of changa, but due to its complex pharmacological actions, involving many neurotransmitter systems, further research is needed in order to establish the specific mechanisms at work.
Ona, G., & Troncoso, S. (2019). Long-lasting analgesic effect of the psychedelic drug changa: A case report. Journal of Psychedelic Studies, 3(1), 7-13., 10.1556/2054.2019.001.
Link to full text
