In 1966, the banning of LSD effectively halted into its effects and therapeutic potential. The Beckley/Imperial research programme, co-founded by DrugScience member Prof. David Nutt, have produced a world-first: brain imaging of volunteers on LSD to investigate what underpins the effects of LSD. The study was widely covered in international media and produced 9 landmark publications which are summarised below.


See the full paper here

This is the first-ever study to examine the effects of LSD on the human brain. Using multiple brain imaging techniques, it gives us the first glimpses into what happens to the brain to produce LSD's psychedelic (and possibly therapeutic) effects.

Why did we do this study?

Hundreds of scientific studies examined the effects of LSD in the 1950s and '60s (when it was still legal), but no study has ever before examined what it does to the brain.

We wanted to know:
• How does LSD so profoundly change consciousness?
• What changes underlie these effects?
• How psychedelics could be therapeutically beneficial?

What did we do?

We gave 20 people either LSD (75µg intravenous) or placebo (saline) on 2 separate days.

• On each day, they completed brain imaging and self- report questionnaires. Brain imaging consisted of:
- Arterial spin labelling - an MRI method to measure blood flow within the brain.
- Resting-state MRI - an MRI while the subject lies still with eyes closed. This acts as a method to assess functional connections within and between brain networks.
- Magnetoencephalography - a method to detect 'brain waves'

What did we find?


All participants reported visual hallucinations and profound changes in consciousness on LSD (vs. placebo).


The brain activity observed is normally associated with visual input.
• Connectivity of brain regions involved in vision ('visual cortex') increased on LSD, so that visual cortex 'talked to' much more of the rest of the brain than after placebo.
• This increase correlated with self-reported hallucinations.
• Changes in brain waves in visual regions also correlated with hallucinations, suggesting these findings are related.
• Blood flow to visual regions also increased.
Note: These are all properties normally associated with visual stimulation, but participants had their eyes closed!


Increased connectivity between brain networks
• Distinct brain networks became more connected to one another — that is, they lost their 'separateness,' allowing for wider and more integrated communication between networks.
• An example of this is the vision finding above, but it occurs across all the brain networks.


Loss of integrity and stability within brain networks
• Brain regions that together make up brain networks lost connectivity with one another, so that 'integrity' within those networks decreased.
• Decreased integrity within a specific network — the Default Mode Network (DMN) — correlated with self-reported 'ego-dissolution' and 'altered meaning.' This suggests that the DMN underlies a stable sense of self and other aspects of normal consciousness.

Why is this important?

Understanding how LSD works in the brain can:
• Help unlock its therapeutic potential.
• Provide valuable information on the mechanisms underlying consciousness and its changing states.


See the full paper here

This is the first study to examine how LSD and music work together to change consciousness

Why did we do this study?

• Music is an effective tool for evoking and studying emotions.
• Psychedelics were used in psychotherapy in the 1950s and 60s. It was believed (but not scientifically evaluated) that music was an important component of this therapy.
• This is the first modern, placebo-controlled study to investigate the hypothesis that psychedelics enhance the emotional response to music.
In this study, we wanted to know:
- Does LSD enhance music-evoked emotions?
- What is the role of music in spiritual-type experiences?

What did we do?

• We gave 10 healthy volunteers either LSD (75µg intravenous) or placebo (saline) on 2 separate days.
• On each day, they listened to 5 tracks of instrumental music (mostly neo-classical and ambient).
• After each track participants were asked: "How emotionally affected were you by the music?".
• Participants also completed questionnaires about specific aspects of their emotional experience: wonder, transcendence, power, tenderness, nostalgia, peacefulness, joyful activation, and tension.
• Finally, participants rated their subjective experience on LSD.

What did we find?


• LSD produced a range of subjective experiences.
• The highest ratings were for the following: "my thoughts wandered freely", "my imagination was extremely vivid", "I felt amazing", "things looked strange" and "I felt an inner warmth".


• People under the effect of LSD reported being significantly more emotionally affected by the music.
• LSD significantly affected the emotions of 'wonder', 'transcendence', 'power' and 'tenderness'.


• The more intense was the overall LSD experience, the more emotionally arousing music felt, the strongest emotion being 'transcendence'.

Why is this important?

• Emotions of transcendence and wonder are traditionally thought of as key aspects of peak and spiritual experiences. The fact that LSD specifically affects these emotions provides an important support the importance of combining both LSD and music for psychotherapy.
• Having spiritual-type or peak experience have been shown to correlate with sustained improvements in well-being and life satisfaction and also with increases in the personality trait of openness.
• Our study supports the view that music is an important element in psychedelic-assisted therapy.


See the full paper here

This study finds that the LSD-induced experience of 'ego-dissolution' results from increased communication and integration across brain systems (networks).

Why did we do this study?

It is well-known that LSD deeply transforms human consciousness — but we don't yet know how these altered states are generated in the brain.
• Our research has shown that psychedelics increase 'cross-talk', and decrease 'separateness', between the different brain networks.
We wanted to know:
What underlies the experience of 'ego-dissolution' — a loss of the sense of 'self' — under LSD?
Is it related to the increased communication across the different brain networks?

What did we do?

• We gave 15 people either LSD (75µg intravenous) or placebo (saline) on 2 separate days.
• On each day, they then completed brain imaging (resting-state fMRI) and self-report questionnaires.
Resting-state fMRI means the subject lies still, with eyes closed, without engaging in a specific task. This is a method to assess functional connections within and between brain networks.
• fMRI data were analysed using 2 techniques: One to calculate functional connectivity density (which measures network connections across different regions of the brain), and another - graph theory analysis (which measures global network integration).

What did we find?

LSD increases functional connectivity across the brain

LSD increased functional connectivity globally, but the strongest effects were seen in the higher-level integrative cortical and sub-cortical structures.
• The areas of the highest increase overlapped with three important networks: default mode network (introspection, sense of self), salience network (switching between tasks) and fronto-parietal network (conscious information access, attention).
• We also found strong overlap between the distribution of the serotonin 2A receptors (key site of action of psychedelic drugs) and the increases in functional connectivity.

Increases in functional connectivity in the regions associated with self-awareness correlate with 'ego-dissolution' scores

• The more connected these separate regions were with other areas, the stronger was the loss of the sense of self.

LSD increases between-system functional connectivity

• LSD not only modifies the intensity of certain functional connections, but also produces qualitatively different connectivity patterns.
• Ego-dissolution scores correlate positively with the increased global integration (or desegregation of neural networks), suggesting that this phenomenon is very important, as the whole brain is affected, not only individual modules.

Why is this important?

• These results provide the evidence that LSD selectively enhances communication between different brain areas and networks maintaining consciousness, diminishing the functional identity of these systems, resulting in the blurring of the borders between the self and environment.
• These results confirm the mechanisms of action of psychedelics formulated from the psilocybin research, namely disintegration (within networks) and desegregation (between networks).
• Our results contrast with the states of 'diminished consciousness' such as deep sleep or anaesthesia, giving further support to the hypothesis that psychedelic state occupies the opposite end of a spectrum of conscious states, defined by their level of entropy or chaos.


See the full paper here

Psychedelics have always presented an apparent paradox: The immediate experience can be unpleasant (accompanied by altered perception, fear, and paranoia), but the experience can also lead to profound and beneficial changes in well-being.

When LSD was first distributed by Sandoz pharmaceuticals in 1948, product guidelines stipulated two main applications:
(1) analytical psychotherapy and
(2) experimental studies on psychoses.
The rationale for the former was that LSD could elicit [the] release of repressed material and provide mental relaxation for anxiety and obsessional neuroses, and, for the latter, that it could model aspects of psychosis.
Albert Hofmann (1980)

We wanted to know:
• How the same compound could a be both a model of, and yet a treatment for, psychopathology.

What did we do?

• We gave 20 volunteers either LSD (75µg) or placebo (saline) on 2 separate days.
• At the end of each dosing session, subjects completed two questionnaires asking about changes in consciousness and psychosis-like symptoms.
• Two weeks after each session, subjects completed three more questionnaires to measure personality traits (including optimism) and delusional thinking.

What did we find?


• The strongest changes were in visual perception (hallucinations).
• Ratings of 'Anxiety' increased the least; the increase in 'Blissful state' was far greater than the increase in anxiety.
• Together, this means subject had an overall pleasant experience.


• Ratings of psychosis-like symptoms increased after LSD, especially 'cognitive disorganisation.'
• Overall, scores on the questionnaire were higher than after sleep deprivation, dreaming, cannabis/THC, or ketamine.
- This suggests that LSD causes strong psychosis-like effects.
Note: Although the questionnaire suggests that subjects' experiences were unpleasant and psychosis-like, the ratings on the consciousness questionnaire show that positive mood and a 'blissful state' were more common and pronounced.


• Personality traits 'Optimism' and 'Openness' were increased 2 weeks after LSD.
• But delusional thinking was not increased (and even showed a slight trend towards a decrease).

• This suggests that the positive effects linger, but the psychosis-like effects do not.


• Psychedelics are thought to fundamentally change the quality of consciousness towards a more unconstrained, chaotic, 'entropic' state. This is hypothesised to be responsible for psychosis-like symptoms and altered perception in the short term.
• However, the same 'loosening' of brain networks results in more flexible patterns of thinking, which may improve well-being in the longer term.
• 'Entropic' cognition may be a more fundamental characteristic of the psychedelic state than either positive or negative mood.

Why is this important?

The study shows that:
1. The immediate effects of psychedelics can be quite different from their longer-term effects, and
2. The long-term effects are what is clinically relevant.
This adds to the evidence base for the therapeutic potential of LSD in the treatment of mood disorders such as depression.


See the full paper here

LSD has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction. It was also explored as an enhancer of mind control. Our study focused on 'primary suggestibility', the induction of thoughts and actions via suggestions.

Why did we do this study?

• This is the first study since the Prohibition to study effects of LSD on suggestibility in a modern, placebo-controlled study. Another objective was to test safety, find the optimal dose for the subsequent neuroimaging study and to check that LSD is well-tolerated.
• Suggestibility has been found to play an important role in treatment of some conditions. Hypnotic suggestion can treat pain, and suggestibility may play a role in psychotherapy. The ability of LSD to enhance suggestibility was first noted by therapists working with LSD in the 1950s and 1960s.

We wanted to know: What effect would LSD have on suggestibility?

What did we do?

We gave 10 people either LSD (40 to 80µg intravenous) or placebo (saline) on 2 separate days. On each day, they then completed suggestibility tasks and self-report questionnaires.
Creative Imagination Scale - Participants were asked to imagine different scenarios such as their outstretched arm becoming heavier, drinking cool refreshing water, that time becomes distorted, etc. We asked participants to rate the intensity of these suggested effects.
Mental Imagery Test = Participants were asked to imagine, with their eyes closed, a succession of sensory experiences such as the taste of honey or the smell of freshly cut grass.
Personality traits were measured using a self-report personality scale (NEO-FFI).

What did we find?

LSD administered in a supportive clinical environment was SAFE and WELL TOLERATED


• Even at the moderate doses used, the vividness/realism of suggested scenarios people were asked to imagine was significantly higher on LSD, compared to placebo.


• The degree of this enhancement correlated with having a conscientious personality.
• Conscientiousness is considered to be related to 'ego' control. It is interesting that people who were most influenced under LSD were those who scored highly on this personality trait, possibly supporting the inference that LSD facilitates suggestibility by temporarily suspending the (very human) drive to maintain control of one's mind and environment.

Why is this important?

• The importance of prior expectations ('set') and environment (`setting') in determining the nature of psychedelics experience is often emphasised.
• However, in the clinical context, another variable is important — the interpretation. Being aware of the influence of suggestion and being able to take this variable into consideration are very important in developing optimal psychedelic-assisted therapies.
• The influence of suggestion in reports of psychedelic-induced mystical or religious experiences deserves more investigation, since the same neurobiological state can be interpreted as profound yet secular by one individual, but mystical by another.


See the full paper here

In this study we find a relationship between our brain imaging results (LSD-induced 'entropy' or 'chaos' in the brain) and changed personality traits 2 weeks later.

Why did we do this study?

• Our research has shown that both psilocybin and LSD increase openness and optimism weeks after the psychedelic experience. This has important clinical implications, supporting psychedelic-assisted psychotherapy.
• Our research has also shown that psychedelics increase 'entropy' (chaos, or disorder) in the brain, 'loosening up' rigid patterns of activity to produce a more flexible cognitive state.
• Here we wanted to know:
- How do psychedelics produce personality changes?
- Is it related to our finding of increased entropy?

What did we do?

• We gave 19 people either LSD (75µg intravenous) or placebo (saline) on 2 separate days.
• On each day, they then completed brain imaging (fMRI) to measure activity during eyes-closed rest and while listening to music.
• fMRI data were analysed using a new technique that calculates 'sample entropy' - a different way of expressing the degree of chaos in the brain induced by LSD.
• We also measured personality traits on 3 occasions: Once at the very beginning of the study (before either LSD or saline), and again 2 weeks after each test session.

What did we find?


• Our measure of 'entropy' (chaotic/erratic brain activity) increased throughout most of the brain.

Increased openness

• Ratings of the personality trait 'openness' (linked to imagination, aesthetic appreciation, non-conformity, creativity) were higher 2 weeks after LSD, but not after placebo.
• This is consistent with the idea that psychedelics may serve as a kind of 'existential shock' therapy, where the profound psychological experience can lead to a change in behaviour and outlook.


• Those subjects showing the greatest brain entropy on LSD had the greatest increase in openness 2 weeks later.
• This relationship was made even stronger by music — that is, it was stronger during the music and post-music scans than pre-music.
• The finding supports the 'Entropic Brain hypothesis' — a theory to explain how and why psychedelics have their effects on the brain and on consciousness.


• Those subjects who reported the greatest amount of 'ego-dissolution' by music (on a post-scan questionnaire) AND showed the greatest increase in entropy (in certain brain networks) were also those who demonstrated the most marked increases in openness.
• This suggests that both music and an 'ego-dissolution' experience may be desirable in a therapeutic context.

Why is this important?

• This is the first time the long-known therapeutic potential of LSD has been directly linked to a biological marker in the brain.
• This helps build the rationale for developing psychedelic therapies, and indicating the beneficial potential of psychedelics and the ways to harness it.


See the full paper here

This is the first study to examine how LSD and music work together to change consciousness and the human brain.

Why did we do this study?

• Music is an effective tool for evoking and studying emotions.
• Psychedelics were used in psychotherapy in the 1950s and 60s. It was believed (but not scientifically evaluated) that music was an important component of this therapy.
• Our previous findings showed that LSD enhances the emotional response to music, creating a deeper and stronger emotional experience.
• In this study, we wanted to know:
- What underlies this difference?
- How does music influence the effect that LSD has on the brain?

What did we do?

• We gave 12 people either LSD (75µg intravenous) or placebo (saline) on 2 separate days.
• On each day, they then completed brain imaging and questionnaires. Brain imaging (fMRI) measured activity during rest and while listening to music.
• Analyses focused on a specific region of the brain: parahippocampal cortex (PHC), which is involved in emotion, memory, and ego/self functions, and has been linked to the response to psychedelics.
• We used 2 analysis types:
- Seed-based analysis - a method of measuring all the functional connections a particular brain region has (in our case parahippocampal cortex).
- Dynamic Causal Modelling - a method to determine the direction of information flow between connected regions.

What did we find?


• Music on LSD (vs. music on placebo) increased connectivity of the PHC (red) with several other regions (yellow/orange) (especially the visual cortex).


• This effect correlated with self-report of 'eyes-closed visions,' including complex images (scenes, etc.) and visions of one's past.
• Together, the findings suggest that music and LSD interact to increase mental imagery of autobiographical nature.

What do we make of this?

• PHC is highly connected with the Default Mode Network (DMN), which exerts top-down control over the PHC. Psychedelics decrease this DMN control, resulting in altered consciousness.
• LSD and music lift the usual top-down control that the DMN holds over the PHC, allowing the PHC to interact more freely with the visual system.
• The input of memories to the visual system — a 'flip' in the normal direction of information flow — may underlie the reported visions.

Why is this important?

The findings emphasise the scientific value of psychedelics in terms of:
• Progressing our understanding of brain function by clarifying the neural circuits involved in visions; and
• Developing a rationale for LSD-assisted psychotherapy by explaining how music — which acts to liberate emotional memories — interacts with LSD to help evoke personal memories and enhance mental imagery.


See the full paper here

Mental time travel refers to the ability to think about future or past, to recollect aspects of past autobiographical episodes or imagine future experiences.

Why did we do this study?

• Spontaneous mental time travel (happening during mind wandering) has been previously linked to an activity in a particular brain network — the Default Mode Network (DMN).
• Our research has shown that both psilocybin and LSD decrease the activity of the DMN. This effect is a key factor in the ability of these substances to induce "ego dissolution," an experience of the loss of the sense of self.
• Research has shown that people with greater connectivity in the DMN tend to reflect on the past more, engage in more ruminative thought, and suffer from depression and general low mood.
• We hypothesised that if LSD reduces mental time travel, through reducing the connectivity within the DMN, it could potentially help people suffering from depression.
• Here we wanted to know:
- How do psychedelics affect mental time travel?
- Does this relate to changes in the connectivity within the DMN?

What did we do?

• We gave 19 people either LSD (75µg intravenous) or placebo (saline) on 2 separate days. On each day, they then completed brain imaging (fMRI) to measure activity during eyes-closed rest.
• After brain imaging participants answered the questions:
‘What was it like in the scanner?',
'Did you daydream in the scanner, and if so, what did you daydream?',
'Was the experience dreamlike at all, and if so, how?',
'Did you experience any personal thoughts or feelings at any point?'.
• The transcripts of their answers (mentation reports) were scored to calculate all the instances referring to the past, present or future, taking into account both grammar and semantics. All 38 reports were scored by independent raters who did not know who or under what drug condition the report had been done.

What did we find?

Reports after LSD were longer

• In general, participants delivered longer reports (in terms of word count) after LSD.

Mental time travel to the past was reduced

• There were significantly fewer references to the past after LSD, compared to placebo — but no difference in terms of references to the future or present

Decreased mental time travel to the past correlated with change in the DMN connectivity

• After LSD, DMN integrity (connectivity within network) was reduced (blue). • Resting state Default Mode Network integrity correlated with the number of references to the past. I.e. the stronger was disintegration within the DMN, the fewer instances of mental time travel to the past were recorded.

Why is this important?

• These outcomes shed light on the cognitive effects of LSD and specifically a decomposition of the 'narrative-self' or 'narrative identity', which is strongly associated with thinking about one's own past.
• The the ability of LSD to act on the DMN — a key neural circuit in depression - could represent a major opportunity for therapists looking for novel methods of combating depression. At present, several mindfulness-based treatments for depression encourage patients to adopt a more present-focused mode of thinking, and the capacity of LSD to inhibit the DMN could potentially help more patients achieve this.
• In future we need to investigate how long after the acute effects of the drug wear off the decrease in mental time travel and effects on the DMN persist.