Addiction Biology
April 1, 2024
Stephan Tap
12 citations
Alcohol use disorder remains a prevalent psychiatric condition with limited treatment options and high relapse rates. Psychedelic-assisted therapy with psilocybin and LSD shows promise but requires lengthy therapist sessions. The short-acting psychedelic 5-MeO-DMT may offer advantages. This review suggests 5-MeO-DMT can induce mystical experiences and ego-dissolution while increasing psychological flexibility and mindfulness, potentially alleviating mood-related comorbidities that drive alcohol use through negative reinforcement. Preliminary evidence indicates 5-MeO-DMT modulates neural oscillations—increases in gamma linked to ego-dissolution, increases in theta linked to psychological flexibility, and increased coherence across frequencies that may reorganize executive control networks. Animal studies show neuroplasticity, anti-inflammatory effects, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5, with implications for alcohol use disorder and comorbid mood conditions.
Addiction Biology
July 1, 2000
L A Aerts, M Mallaret, H Rigter
12 citations
MBDB, the alpha-ethyl homologue of MDMA, increases serotonin release and inhibits serotonin and noradrenaline re-uptake in the rat brain, though MDMA is more potent. MBDB may slightly increase dopamine release and inhibit its re-uptake, but to a lesser extent than MDMA. Its neuroendocrine effects resemble those of MDMA, raising plasma ACTH, corticosterone, prolactin, and renin. Neurophysiologically, MBDB decreases electrical activity across the brain, especially in alpha 2 and delta bands, unlike hallucinogens which increase alpha 1 activity. In humans, MBDB induces a pleasant introspective state with facilitated communication and empathy, but with slower onset, less euphoria, and fewer stimulant properties than MDMA.
Addiction Biology
September 1, 2020
Ross Van de Wetering, Susan Schenk
9 citations
Repeated exposure to MDMA (ecstasy) causes long-lasting changes in the brain, particularly accumulation of the protein ΔFosB in several regions. In male rats, MDMA self-administration significantly increased ΔFosB in the nucleus accumbens core, parts of the caudate-putamen, several cortical areas, and the amygdala, but not in other striatal regions. Pretreatment with MDMA enhanced the drug's locomotor-activating effect only when injected into the nucleus accumbens or medial caudate-putamen, matching the ΔFosB pattern. These findings resemble those seen with other addictive drugs, suggesting common neuroplastic changes underlying addiction.
Addiction Biology
August 4, 2022
Klára Šíchová, Kateřina Syrová, Edita Kofroňová et al.
8 citations
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.
Addiction Biology
March 1, 2026
Leah M Salinsky, Kyra C Diaz, Joshua L Fox et al.
1 citation
Polysubstance use of opioids and stimulants is common, but most research examines each drug alone. In rats, the effects of fentanyl and methamphetamine—alone or combined—on movement sensitization and social behavior depended on drug class, drug history, and sex. After withdrawal, social deficits emerged. A single dose of the psychedelic DOI reversed those social deficits and even boosted social interaction in females. The findings suggest psychedelics might help treat social impairments linked to withdrawal from combined opioid and stimulant use.
Addiction Biology
March 1, 2025
Salar Sabziparvar, Kazem Khodaei, Javad Tolouei Azar
1 citation
Moderate-intensity continuous training (MICT) reduces apoptosis and oxidative damage in the cerebral cortex of rats with chronic ketamine abuse. In a study of 24 Wistar rats, those receiving 50 mg/kg/day ketamine for 8 weeks and then undergoing 8 weeks of MICT showed significantly fewer apoptotic cells and lower expression of pro-apoptotic proteins Bax and caspase-3, along with higher anti-apoptotic Bcl-2, compared to rats that only withdrew from ketamine without exercise. MICT also decreased oxidative stress markers (8-oxo-2'-deoxyguanosine) and increased antioxidant enzymes glutathione peroxidase and glutathione reductase, as well as nitric oxide. Levels of malondialdehyde, myeloperoxidase, glutathione, superoxide dismutase, and catalase did not differ between groups. The findings suggest exercise can mitigate ketamine-induced brain damage.
Addiction Biology
March 1, 2026
Isis Koutrouli, Vojtěch Brejtr, Marek Schwendt et al.
Psilocybin and ibogaine, given in a dose-escalation protocol, facilitated extinction learning in male rats that had self-administered cocaine. Psilocybin reduced active lever pressing one day after the second dose, with a nonsignificant reduction after the first dose; ibogaine significantly reduced pressing even after the first administration. Neither drug significantly altered cue-induced reinstatement of drug-seeking, though psilocybin showed a trend toward attenuation. The treatments had no side effects on general locomotor activity or anxiety-like behavior in the open field test. These results suggest psilocybin and ibogaine may support extinction learning and possibly protect against relapse, warranting further research into their antiaddictive potential.
Addiction Biology
August 1, 2025
Natalia M Kleinhans, Garth E Terry, Dahyeon Kang et al.
Exposure to multimodal cannabis cues (visual and olfactory) alters resting-state functional connectivity between the ventral tegmental area (VTA) and the striatum in regular cannabis users. In a preliminary fMRI study of 28 regular cannabis users and 26 controls, no group differences in VTA-striatal connectivity were observed at baseline. After cue exposure, cannabis users showed significantly greater VTA-caudate connectivity than controls. Among cannabis users, baseline craving positively correlated with VTA-striatal connectivity both before and after cue exposure. These findings suggest a neural mechanism by which drug cues may increase relapse vulnerability even after cues are removed.
Addiction Biology
February 1, 2025
Kellen M McDonald, Mikki Schantell, Jason A John et al.
Chronic cannabis use is linked to altered coordination between visual brain regions and the ventral attention network during cognitive flexibility tasks. Twenty-five chronic users and 30 non-users completed a task-switch paradigm while undergoing magnetoencephalography. Users showed modified associations between functional connectivity switch costs and behavioral switch costs along pathways connecting visual cortices and attention-related regions, within theta, alpha, and gamma frequency ranges. These findings indicate that cannabis use is associated with changes in how brain networks communicate during tasks requiring cognitive flexibility, particularly involving visual and executive function areas.
Addiction Biology
January 1, 2022
Laurel P Gibson, Hollis C Karoly, Jarrod M. Ellingson et al.
Cannabis flower with both THC and CBD produces similar positive effects but less paranoia and anxiety than THC-dominant cannabis. In a naturalistic at-home study, 159 regular cannabis users were randomly assigned to one of three chemovars: THC-dominant (24% THC, 1% CBD), THC+CBD (9% THC, 10% CBD), or CBD-dominant (1% THC, 23% CBD). Plasma samples showed those using the CBD-dominant or THC+CBD chemovars had significantly less THC and more CBD than those using the THC-dominant chemovar. The THC+CBD chemovar yielded similar positive subjective effects but significantly less paranoia and anxiety compared to the THC-dominant chemovar, suggesting potential harm reduction from CBD.
Addiction Biology
November 1, 2020
The hallucinogen 25B-NBOMe produced rewarding and reinforcing effects in rats, as shown by conditioned place preference and self-administration tests. Blocking dopamine D1 or D2 receptors prevented these effects, while blocking serotonin 2A receptors did not. 25B-NBOMe increased dopamine levels and altered expression of dopamine-related proteins in brain reward regions. It also induced head twitch responses and altered delta and gamma brain wave activity, effects that were normalized by dopamine receptor antagonists. These findings suggest 25B-NBOMe has abuse potential mediated through the dopaminergic system.
Addiction Biology
December 1, 2005
Shannon C Miller
Dextromethorphan (DM), an over-the-counter cough medicine available in over 140 preparations, can cause addiction, psychosis, and withdrawal when abused at greater than indicated doses. A case of DM dependence with rarely published complications is described, based on an interview with the individual and a review of medical databases. DM and its active metabolite dextrorphan (DOR) have specific biological features of addiction and can induce psychiatric sequelae. DOR has pharmacodynamic properties similar to dissociatives and may be more responsible for the dissociative effect sought by abusers, but also carries risks of life-threatening psychoses, dissociative-induced accidents, and addiction. Health-care providers appear largely unaware of DM's toxidrome and addiction liability.