Psychedelic drugs are a focus of interest in the treatment of depression and other disorders but there are longstanding concerns about possible adverse psychiatric consequences. Because the relevant literature is largely informal, the seriousness of these risks is difficult to evaluate.

Searches were made for case reports of schizophrenia-spectrum, affective or other psychiatric disorders after use of psychedelic drugs. Case reports of flashbacks were also searched for. Individuals with recent use of other drugs (apart from cannabis and alcohol) and/or a previous history of major psychiatric disorder were excluded. Symptoms were tabulated using the Syndrome Check List of the Present State Examination (PSE-9).

We found 17 case reports of schizophrenia spectrum disorder, 17 of affective disorder (depression, mania, or both), 3 cases of anxiety, 1 of depersonalization, and 1 of unclassifiable illness. The states could develop after a single use of the drug (5/17 schizophrenia; 6/17 affective disorder), and duration was highly variable. Recovery was the rule in cases of affective disorder but not in schizophrenia spectrum disorder. Twelve of 29 cases of flashbacks showed psychiatric symptomatology definitely outlasting the attacks, mainly anxiety (5 cases) and depression (8 cases). Flashback symptoms resolved within twelve months in approximately half of the cases but in a few persisted for years.

Reliable descriptions of schizophrenia spectrum disorder and major affective disorder after psychedelic drug use disorder exist but are relatively uncommon. Flashbacks are sometimes but not always associated with psychiatric symptomatology, mainly anxiety or depression.

Posttraumatic stress disorder (PTSD) is reliably associated with reduced brain volume relative to healthy controls, in areas similar to those found in depression. We investigated whether in a PTSD sample brain volumes in these areas were related to reporting specific symptoms of PTSD or to overall symptom severity.

Structural MRI scans were obtained from 28 participants diagnosed with PTSD according to DSM-IV-TR. Participants reported the extent of individual PTSD symptoms using the Posttraumatic Diagnostic Scale. Voxel-based morphometry applying the Dartel algorithm implemented within SPM5 was used to identify volumetric changes, related to PTSD total, symptom cluster, and individual symptom scores.

Brain volume was unrelated to overall PTSD severity, but greater reexperiencing scores predicted reduced volumes in the middle temporal and inferior occipital cortices. Increased reports of flashbacks predicted reduced volume in the insula/parietal operculum and in the inferior temporal gyrus.

The data illustrate the value of analyses at the symptom level within a patient population to supplement group comparisons of patients and healthy controls. Areas identified were consistent with a neurobiological account of flashbacks implicating specific abnormalities in the ventral visual stream.

A hallmark symptom after psychological trauma is the presence of intrusive memories. It is unclear why only some moments of trauma become intrusive, and how these memories involuntarily return to mind. Understanding the neural mechanisms involved in the encoding and involuntary recall of intrusive memories may elucidate these questions.

Participants (n = 35) underwent functional magnetic resonance imaging (fMRI) while being exposed to traumatic film footage. After film viewing, participants indicated within the scanner, while undergoing fMRI, if they experienced an intrusive memory of the film. Further intrusive memories in daily life were recorded for 7 days. After 7 days, participants completed a recognition memory test. Intrusive memory encoding was captured by comparing activity at the time of viewing ‘Intrusive scenes’ (scenes recalled involuntarily), ‘Control scenes’ (scenes never recalled involuntarily) and ‘Potential scenes’ (scenes recalled involuntarily by others but not that individual). Signal change associated with intrusive memory involuntary recall was modelled using finite impulse response basis functions.

We found a widespread pattern of increased activation for Intrusive v. both Potential and Control scenes at encoding. The left inferior frontal gyrus and middle temporal gyrus showed increased activity in Intrusive scenes compared with Potential scenes, but not in Intrusive scenes compared with Control scenes. This pattern of activation persisted when taking recognition memory performance into account. Intrusive memory involuntary recall was characterized by activity in frontal regions, notably the left inferior frontal gyrus.

The left inferior frontal gyrus may be implicated in both the encoding and involuntary recall of intrusive memories.

Psychological traumatic events, such as war or road traffic accidents, are widespread. A small but significant proportion of survivors develop post-traumatic stress disorder (PTSD). Distressing, sensory-based involuntary memories of trauma (henceforth ‘flashbacks’) are the hallmark symptom of PTSD. Understanding the development of flashbacks may aid their prevention. This work is the first to combine the trauma film paradigm (as an experimental analogue for flashback development) with neuroimaging to investigate the neural basis of flashback aetiology. We investigated the hypothesis that involuntary recall of trauma (flashback) is determined during the original event encoding.

A total of 22 healthy volunteers viewed a traumatic film whilst undergoing functional magnetic resonance imaging (fMRI). They kept a 1-week diary to record flashbacks to specific film scenes. Using a novel prospective fMRI design, we compared brain activation for those film scenes that subsequently induced flashbacks with both non-traumatic control scenes and scenes with traumatic content that did not elicit flashbacks (‘potentials’).

Encoding of scenes that later caused flashbacks was associated with widespread increases in activation, including in the amygdala, striatum, rostral anterior cingulate cortex, thalamus and ventral occipital cortex. The left inferior frontal gyrus and bilateral middle temporal gyrus also exhibited increased activation but only relative to ‘potentials’. Thus, these latter regions appeared to distinguish between traumatic content that subsequently flashed back and comparable content that did not.

Results provide the first prospective evidence that the brain behaves differently whilst experiencing emotional events that will subsequently become involuntary memories – flashbacks. Understanding the neural basis of analogue flashback memory formation may aid the development of treatment interventions for this PTSD feature.