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Psychiatry & Medicine

Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents

Abstract

A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.
Du, H., Tian, S., Chen, J., Gu, H., Li, N., & Wang, J. (2016). Synthesis and biological evaluation of N 9-substituted harmine derivatives as potential anticancer agents. Bioorganic & medicinal chemistry letters26(16), 4015-4019. 10.1016/j.bmcl.2016.06.087
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As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage

Khalid, F., Kowsika, S., Ghobrial, I., & Rehman, S. (2016). As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage. In A46. LUNG DISEASE DUE TO OTC AND ILLICITS: CASE REPORTS (pp. A1616-A1616). American Thoracic Society.
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Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey

Abstract

Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.

Schindler, E. A., Gottschalk, C. H., Weil, M. J., Shapiro, R. E., Wright, D. A., & Sewell, R. A. (2015). Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey. Journal of psychoactive drugs, 1-10. http://dx.doi.org/10.1080/02791072.2015.1107664

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“Herbal seizures” – atypical symptoms after ibogaine intoxication: a case report

Abstract

INTRODUCTION:

Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse.

CASE PRESENTATION:

We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative.

CONCLUSIONS:

Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

Breuer, L., Kasper, B. S., Schwarze, B., Gschossmann, J. M., Kornhuber, J., & Müller, H. H. (2015). “Herbal seizures”–atypical symptoms after ibogaine intoxication: a case report. Journal of medical case reports, 9(1), 1-5. http://dx.doi.org/10.1186/s13256-015-0731-4
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"Herbal seizures" – atypical symptoms after ibogaine intoxication: a case report

Abstract

INTRODUCTION:

Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse.

CASE PRESENTATION:

We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative.

CONCLUSIONS:

Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

Breuer, L., Kasper, B. S., Schwarze, B., Gschossmann, J. M., Kornhuber, J., & Müller, H. H. (2015). “Herbal seizures”–atypical symptoms after ibogaine intoxication: a case report. Journal of medical case reports, 9(1), 1-5. http://dx.doi.org/10.1186/s13256-015-0731-4
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Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease?

Abstract

Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.

Djamshidian, A., Bernschneider‐Reif, S., Poewe, W., & Lees, A. J. (2015). Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease?. Movement Disorders Clinical Practice. http://dx.doi.org/10.1002/mdc3.12242
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Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?

Abstract

Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.

Djamshidian, A., Bernschneider‐Reif, S., Poewe, W., & Lees, A. J. (2015). Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease?. Movement Disorders Clinical Practice. http://dx.doi.org/10.1002/mdc3.12242
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Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress

Abstract

Herpes simplex virus types 1 and 2 (HSV-1 and -2) are highly prevalent in many populations and therapeutic options are limited. Both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. Primary or recurrent HSV infections may lead to deleterious outcomes: HSV-1 infection may result in corneal blindness and encephalitis and HSV-2 infection leads to herpes genitalis. While no effective vaccine is available, acyclovir is widely used for therapy, which targets and inhibits viral DNA polymerase. Although acyclovir is of low toxicity, resistant strains arise due to persistent use, mainly in immune compromised patients. In our effort to identify new HSV inhibitory molecules, harmine was found to potently inhibit HSV infection. Harmine, a beta-carbon alkaloid with an indole core structure and a pyridine ring, is widely distributed in plants. Earlier studies showed that harmine exhibited pharmacological activities such as antifungal, antimicrobial, antitumor, antiplasmodial and antioxidants. In the current study, we showed that harmine was a potent inhibitor of HSV-2 infection in vitro assays with EC50 value at around 1.47μM and CC50 value at around 337.10μM. The HSV RNA transcription, protein synthesis, and virus titers were reduced by the presence of harmine in a dose dependent manner. Further study on the mechanism of the anti-HSV activity showed that harmine blocked HSV-induced ROS production and the upregulated cytokine/chemokine expression, but our evidence showed that the inhibition of viral replication was unlikely mediated by the blocking of ROS production. We demonstrated that harmine significantly reduced HSV-2-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. We found that harmine also inhibited HSV-2-mediated p38 kinase and c-Jun N-terminal kinases (JNK) phosphorylation.

Chen, D., Su, A., Fu, Y., Wang, X., Lv, X., Xu, W., … & Wu, Z. (2015). Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress. Antiviral research, 123, 27-38. 10.1016/j.antiviral.2015.09.003
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The potential utility of some legal highs in CNS disorders

Abstract

Over the last decade there has been an explosion of new drugs of abuse, so called legal highs or novel psychoactive substances (NPS). Many of these abused drugs have unknown pharmacology, but their biological effects can be anticipated from their molecular structure and possibly also from online user reports. When considered with the findings that some prescription medications are increasingly abused and that some abused drugs have been tested clinically one could argue that there has been a blurring of the line between drugs of abuse and clinically used drugs. In this review we examine these legal highs/NPS and consider whether, based on their known or predicted pharmacology, some might have the potential to be clinically useful in CNS disorders.

Davidson, C., & Schifano, F. (2015). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.07.010
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Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

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interested in becoming a trained psychedelic-assisted therapist?