OPEN Foundation

New substances

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

June 5, 2017 / LSD, Neuroscience, New substances, Other substances, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as “research chemicals” or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, HPLC diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans.
Brandt, S. D., Kavanagh, P. V., Twamley, B., Westphal, F., Elliott, S. P., Wallach, J., … & Halberstadt, A. L. (2017). Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775). Drug Testing and Analysis. 10.1002/dta.2222
Link to full text

Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile

May 18, 2017 / LSD, New substances, Other substances, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
Link to full text

Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile

May 18, 2017 / LSD, New substances, Other substances, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
Link to full text

A single administration of the hallucinogen, 4-acetoxy-dimethyltryptamine, prevents the shift to a drug-dependent state and the expression of withdrawal aversions in rodents

May 4, 2017 / Addiction, Mushrooms / Psilocybin, Neuroscience, New substances, Papers, Psychiatry, Psychology, Psychopharmacology / By / , , , , ,

Abstract

Despite several studies suggesting the therapeutic use of 5-hydroxytryptamine receptors type 2A (5-HT2A) agonists in the treatment of substance use disorders, the neurobiological basis accounting for such effects are still unknown. It has been observed that chronic exposure to drugs of abuse produces molecular and cellular adaptations in ventral tegmental area (VTA) neurons, mediated by brain-derived neurotrophic factor (BDNF). These BDNF-induced adaptations in the VTA are associated with the establishment of aversive withdrawal motivation that leads to a drug-dependent state. Growing evidence suggests that 5-HT2A receptor signaling can regulate the expression of BDNF in the brain. In this study, we observed that a single systemic or intra-VTA administration of a 5-HT2A agonist in rats and mice blocks both the aversive conditioned response to drug withdrawal and the mechanism responsible for switching from a drug-naive to a drug-dependent motivational system. Our results suggest that 5-HT2A agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.
Vargas‐Perez, H., Grieder, T. E., Ting‐A‐Kee, R., Maal‐Bared, G., Chwalek, M., & van der Kooy, D. (2017). A single administration of the hallucinogen, 4‐acetoxy‐dimethyltryptamine, prevents the shift to a drug‐dependent state and the expression of withdrawal aversions in rodents. European Journal of Neuroscience. 10.1111/ejn.13572
Link to full text

LSD instead of 25I-NBOMe: The revival of LSD? A case report

February 27, 2017 / Chemistry, LSD, Medicine, New substances, Other substances, Papers, Publications, Safety, Toxicology / By / , , , , , ,

Abstract

Observation: We report a case of a 25-year-old man crushed by a train while he was returning from a rave party. The consumption of 25I-NBOMe was rapidly evoked by people who had participated at the party.

Materials and methods: In this context, the post-mortem toxicological expertise was completed by a broad screening using high-resolution mass spectrometry detection (LC-HRMS). Three hundred NPS and metabolites (including 25B, 25C and 25I-NBOMes) can be found with this method. A targeted screening in MRM mode was also performed on a smaller number of hallucinogens.

Results: The toxicological analyses were performed on blood and urine samples. Amphetamines, cocaine, cannabinoids and opiates were not detected. Ethanol was measured at 0.71 g/L and 1.59 g/L in blood and urine samples, respectively. The screening by LC-HRMS did not reveal the presence of NPS, including NBOMes. The targeted screening in MRM mode revealed the presence of LSD and its metabolite, the 2-oxo-3-hydroxy-LSD. LSD was quantified at 0.2 ng/mL in blood.

Conclusion: This case alerts on the frequent confusion between NBOMes and LSD and on the renewed interest for LSD due to the popularity of NBOMes. This case therefore encourages the prudence and research of all hallucinogenic substances, even when the context is evocative.

Bodeau, S., Bennis, Y., Régnaut, O., Fabresse, N., Richeval, C., Humbert, L., … & Lemaire-Hurtel, A. S. (2017). LSD instead of 25I-NBOMe: The revival of LSD? A case report. Toxicologie Analytique et Clinique, 29(1), 139-143. 10.1016/j.toxac.2016.12.007
Link to full text

"Being with a Buddha": A Case Report of Methoxetamine Use in a United States Veteran with PTSD

January 29, 2017 / Anxiety disorders / PTSD, Ketamine, New substances, Papers, Psychology / By / , ,

Abstract

Methoxetamine (MXE) is a ketamine analogue with a high affinity for the N-methyl-D-aspartate (NMDA) receptor. MXE is a newly emerging designer drug of abuse and is widely available through on-line sources and is not detected by routine urine drug screens. In this report, we describe a United States (US) veteran with posttraumatic stress disorder (PTSD) and heavy polysubstance use, who injected high dose MXE for its calming effect. Given MXE’s structural similarities to ketamine and recent work showing that ketamine reduces PTSD symptoms, we hypothesize that MXE alleviated this veteran’s PTSD symptoms through action at the NMDA receptor and via influences on brain-derived neurotrophic factor (BDNF). To our knowledge, this is the first case report of self-reported use of MXE in the US veteran population. More awareness of designer drugs, such as MXE, is an important first step in engaging patients in the treatment of designer drug addiction in both military/veteran settings and civilian settings.
Striebel, J. M., Nelson, E. E., & Kalapatapu, R. K. (2017). “Being with a Buddha”: A Case Report of Methoxetamine Use in a United States Veteran with PTSD. Case reports in psychiatry, 2017. 10.1155/2017/2319094
Link to full text

“Being with a Buddha”: A Case Report of Methoxetamine Use in a United States Veteran with PTSD

January 29, 2017 / Anxiety disorders / PTSD, Ketamine, New substances, Papers, Psychology / By / , ,

Abstract

Methoxetamine (MXE) is a ketamine analogue with a high affinity for the N-methyl-D-aspartate (NMDA) receptor. MXE is a newly emerging designer drug of abuse and is widely available through on-line sources and is not detected by routine urine drug screens. In this report, we describe a United States (US) veteran with posttraumatic stress disorder (PTSD) and heavy polysubstance use, who injected high dose MXE for its calming effect. Given MXE’s structural similarities to ketamine and recent work showing that ketamine reduces PTSD symptoms, we hypothesize that MXE alleviated this veteran’s PTSD symptoms through action at the NMDA receptor and via influences on brain-derived neurotrophic factor (BDNF). To our knowledge, this is the first case report of self-reported use of MXE in the US veteran population. More awareness of designer drugs, such as MXE, is an important first step in engaging patients in the treatment of designer drug addiction in both military/veteran settings and civilian settings.
Striebel, J. M., Nelson, E. E., & Kalapatapu, R. K. (2017). “Being with a Buddha”: A Case Report of Methoxetamine Use in a United States Veteran with PTSD. Case reports in psychiatry, 2017. 10.1155/2017/2319094
Link to full text

Pharmacology and Toxicology of N-Benzylphenethylamine (“NBOMe”) Hallucinogens

January 18, 2017 / Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Publications, Toxicology / By /

Abstract

Serotonergic hallucinogens induce profound changes in perception and cognition. The characteristic effects of hallucinogens are mediated by 5-HT2A receptor activation. One class of hallucinogens are 2,5-dimethoxy-substituted phenethylamines, such as the so-called 2C-X compounds 2,5-dimethoxy-4-bromophenethylamine (2C-B) and 2,5-dimethoxy-4-iodophenethylamine (2C-I). Addition of an N-benzyl group to phenethylamine hallucinogens produces a marked increase in 5-HT2A-binding affinity and hallucinogenic potency. N-benzylphenethylamines (“NBOMes”) such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) show subnanomolar affinity for the 5-HT2A receptor and are reportedly highly potent in humans. Several NBOMEs have been available from online vendors since 2010, resulting in numerous cases of toxicity and multiple fatalities. This chapter reviews the structure–activity relationships, behavioral pharmacology, metabolism, and toxicity of members of the NBOMe hallucinogen class. Based on a review of 51 cases of NBOMe toxicity reported in the literature, it appears that rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, an effect that may be linked to NBOMe-induced seizures, hyperthermia, and vasoconstriction.

Halberstadt, A. L. (2016). Pharmacology and Toxicology of N-Benzylphenethylamine (“NBOMe”) Hallucinogens. 10.1007/7854_2016_64

Link to full text

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats

November 30, 2016 / Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Safety / By / , , , ,

Abstract

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, ‘foxy’) is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.
Noworyta-Sokołowska, K., Kamińska, K., Kreiner, G., Rogóż, Z., & Gołembiowska, K. (2016). Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats. Neurotoxicity research, 30(4), 606-619. 10.1007/s12640-016-9654-0
Link to full text

Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ)

June 6, 2016 / LSD, Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the ‘research chemicals’/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6 J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 µg/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50 = 114.2 nmol/kg) was equipotent to LSD (ED50 = 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50  = 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Elliott, S. P., Wallach, J., Colestock, T., … & Halberstadt, A. L. (2016). Return of the lysergamides. Part II: Analytical and behavioural characterization of N6‐allyl‐6‐norlysergic acid diethylamide (AL‐LAD) and (2’S, 4’S)‐lysergic acid 2, 4‐dimethylazetidide (LSZ). Drug testing and analysis. http://dx.doi.org/10.1002/dta.1985
Link to full text

7 May - Psychedelics, Nature & Mental Health with Sam Gandy

REGISTER NOW!
X