Speculative use cases for psychedelics as therapies under different mechanistic models, with SEBUS effects hypothesized to predominate with microdosing, and a combination of SEBUS and REBUS effects with macrodosing.
| . | SEBUS effects . | REBUS effects . | ALBUS (powerfully altering internal working models) . |
|---|---|---|---|
| Depression | Behavioral activation; increased ability to imagine and experience positive outcomes | Interrupting depressogenic patterns of cognition and behavior (e.g. rumination) | Microdosing for behavioral activation Macrodosing for cognitive restructuring |
| Anxiety | Potential improvements through increased confidence, but possibly maladaptive effects due to greater vividness of negative imaginings | Reducing the grip of anxiety-provoking beliefs | Microdosing for increasing confidence, and possibly as an adjunct to exposure interventions Macrodosing for flooding and reconsolidation |
| Creativity | Both divergent and convergent creativity potentially elevated through enhanced associations and cognitive control | More divergent creativity through freer associations | Microdosing for either convergent or divergent creativity Macrodosing for divergent creativity |
| Autism spectrum | Potentially beneficial through reducing the gain on excessive prediction errors and increasing the gain on central integrative processes, but possibly contraindicated if accompanied by tendencies toward anxiety | Potentially beneficial for reducing overly rigid patterns and increasing cognitive flexibility, potentially insight | Microdosing for enhanced empathy and attenuated sensory sensitivity Macrodosing for breaking free of rigid patterns and promoting self/other awareness and insight |
| Schizophrenia spectrum | Likely contraindicated, unless condition is driven by functional disconnection, in which case some strengthening of beliefs could be beneficial | Potentially desirable for reducing some forms of delusions based on self-reinforcing beliefs; contraindicated if condition is driven by functional disconnection | Microdosing for enhancing executive functions Macrodosing as last-line intervention; possible protective effects for prodrome through enhancing integration, and possibly inoculation with respect to epistemic hygiene |
| Traumatic brain injury | Potentially protective by encouraging sustained cognitive engagement, preventing learned nonuse, and promoting neuroplasticity | Potentially useful for processing distress and maladaptive cognition and behavior patterns (e.g. cognitive avoidance and activity avoidance) | Microdosing for aiding recovery Macrodosing for breaking through maladaptive patterns to make room for new ones; may also be most beneficial for opening plasticity windows |
| Cognitive decline | Potentially beneficial for similar reasons to those described for traumatic brain injury | Potentially beneficial for similar reasons to those described for traumatic brain injury | Microdosing for prevention Macrodosing for condition management (and possibly prevention if avoidance contributes to cognitive reserve depletion) |
| Wakefulness disorders | Potentially highly beneficial by increasing consciousness level | Potentially beneficial if relaxed beliefs indirectly produce arousal through increased prediction errors | Microdosing for conditions such as narcolepsy Macrodosing as potentially beneficial for coma and persistent vegetative states |
| Addiction | Potentially contraindicated, unless microdosing provides an effective substitution for more addictive substances; increased abilities to visualize consequences/goals and greater connections to values could aid in resisting overly steep discounting of future utility | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as potential substitute for stimulants Macrodosing as potentially beneficial for all addictions |
| Personality disorders | Likely contraindicated as a standalone treatment, but potentially beneficial in conjunction with psychotherapy | Potentially beneficial via insight, unless psychedelic experiences promote spiritual bypassing or destabilize already weakened self-processes | Microdosing as adjunct to psychotherapy Macrodosing for updating maladaptive internal working models; potentially more effective with guided sessions |
| Post-traumatic stress disorder | Potentially contraindicated outside of exposure therapies due to risk of enhancing traumatic imaginings Possibly beneficial if other beliefs are allowed to more effectively compete with dominance from self-traumatizing internal models | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as adjunct for gradual exposure therapies Macrodosing for flooding and compassion-based protocols |
| Chronic pain | Likely highly variable across individuals, with some experiencing undesirable strengthening of pain-enhancing patterns of cognition, and others experiencing potentially beneficial reward-related analgesia (above and beyond anti-inflammatory properties associated with 5-HT2a receptors); possibly effective as adjunct to hypnosis-based interventions | Potentially beneficial for disrupting self-reinforcing patterns of pain-enhancing cognition; possibly temporarily harmful if reduced gating of prediction errors exacerbates pain sensations | Microdosing for reward-related analgesia and anti-inflammatory effects Macrodosing for enhancing self-compassion and acceptance |
| Terminal illness | Potentially helpful by strengthening access to sources of meaning from core values and transpersonal connection | Potentially beneficial by weakening schemas involving death anxiety | Microdosing for increased engagement with life Macrodosing for greater acceptance, connecting to higher meanings, and hopefully beneficial (and possibly transcendent) changes in worldview |
| Existential anxiety | Potentially helpful for similar reasons to those involved in overcoming distress from terminal illness | Potentially beneficial if connections to meaning are actively blocked by preexisting schemas | Microdosing for greater sense of agency, engagement with life, and connection to meanings Macrodosing as potentially beneficial for similar reasons to those involved with terminal illness |
| . | SEBUS effects . | REBUS effects . | ALBUS (powerfully altering internal working models) . |
|---|---|---|---|
| Depression | Behavioral activation; increased ability to imagine and experience positive outcomes | Interrupting depressogenic patterns of cognition and behavior (e.g. rumination) | Microdosing for behavioral activation Macrodosing for cognitive restructuring |
| Anxiety | Potential improvements through increased confidence, but possibly maladaptive effects due to greater vividness of negative imaginings | Reducing the grip of anxiety-provoking beliefs | Microdosing for increasing confidence, and possibly as an adjunct to exposure interventions Macrodosing for flooding and reconsolidation |
| Creativity | Both divergent and convergent creativity potentially elevated through enhanced associations and cognitive control | More divergent creativity through freer associations | Microdosing for either convergent or divergent creativity Macrodosing for divergent creativity |
| Autism spectrum | Potentially beneficial through reducing the gain on excessive prediction errors and increasing the gain on central integrative processes, but possibly contraindicated if accompanied by tendencies toward anxiety | Potentially beneficial for reducing overly rigid patterns and increasing cognitive flexibility, potentially insight | Microdosing for enhanced empathy and attenuated sensory sensitivity Macrodosing for breaking free of rigid patterns and promoting self/other awareness and insight |
| Schizophrenia spectrum | Likely contraindicated, unless condition is driven by functional disconnection, in which case some strengthening of beliefs could be beneficial | Potentially desirable for reducing some forms of delusions based on self-reinforcing beliefs; contraindicated if condition is driven by functional disconnection | Microdosing for enhancing executive functions Macrodosing as last-line intervention; possible protective effects for prodrome through enhancing integration, and possibly inoculation with respect to epistemic hygiene |
| Traumatic brain injury | Potentially protective by encouraging sustained cognitive engagement, preventing learned nonuse, and promoting neuroplasticity | Potentially useful for processing distress and maladaptive cognition and behavior patterns (e.g. cognitive avoidance and activity avoidance) | Microdosing for aiding recovery Macrodosing for breaking through maladaptive patterns to make room for new ones; may also be most beneficial for opening plasticity windows |
| Cognitive decline | Potentially beneficial for similar reasons to those described for traumatic brain injury | Potentially beneficial for similar reasons to those described for traumatic brain injury | Microdosing for prevention Macrodosing for condition management (and possibly prevention if avoidance contributes to cognitive reserve depletion) |
| Wakefulness disorders | Potentially highly beneficial by increasing consciousness level | Potentially beneficial if relaxed beliefs indirectly produce arousal through increased prediction errors | Microdosing for conditions such as narcolepsy Macrodosing as potentially beneficial for coma and persistent vegetative states |
| Addiction | Potentially contraindicated, unless microdosing provides an effective substitution for more addictive substances; increased abilities to visualize consequences/goals and greater connections to values could aid in resisting overly steep discounting of future utility | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as potential substitute for stimulants Macrodosing as potentially beneficial for all addictions |
| Personality disorders | Likely contraindicated as a standalone treatment, but potentially beneficial in conjunction with psychotherapy | Potentially beneficial via insight, unless psychedelic experiences promote spiritual bypassing or destabilize already weakened self-processes | Microdosing as adjunct to psychotherapy Macrodosing for updating maladaptive internal working models; potentially more effective with guided sessions |
| Post-traumatic stress disorder | Potentially contraindicated outside of exposure therapies due to risk of enhancing traumatic imaginings Possibly beneficial if other beliefs are allowed to more effectively compete with dominance from self-traumatizing internal models | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as adjunct for gradual exposure therapies Macrodosing for flooding and compassion-based protocols |
| Chronic pain | Likely highly variable across individuals, with some experiencing undesirable strengthening of pain-enhancing patterns of cognition, and others experiencing potentially beneficial reward-related analgesia (above and beyond anti-inflammatory properties associated with 5-HT2a receptors); possibly effective as adjunct to hypnosis-based interventions | Potentially beneficial for disrupting self-reinforcing patterns of pain-enhancing cognition; possibly temporarily harmful if reduced gating of prediction errors exacerbates pain sensations | Microdosing for reward-related analgesia and anti-inflammatory effects Macrodosing for enhancing self-compassion and acceptance |
| Terminal illness | Potentially helpful by strengthening access to sources of meaning from core values and transpersonal connection | Potentially beneficial by weakening schemas involving death anxiety | Microdosing for increased engagement with life Macrodosing for greater acceptance, connecting to higher meanings, and hopefully beneficial (and possibly transcendent) changes in worldview |
| Existential anxiety | Potentially helpful for similar reasons to those involved in overcoming distress from terminal illness | Potentially beneficial if connections to meaning are actively blocked by preexisting schemas | Microdosing for greater sense of agency, engagement with life, and connection to meanings Macrodosing as potentially beneficial for similar reasons to those involved with terminal illness |
This table is neither meant to be exhaustive nor definitive.
Speculative use cases for psychedelics as therapies under different mechanistic models, with SEBUS effects hypothesized to predominate with microdosing, and a combination of SEBUS and REBUS effects with macrodosing.
| . | SEBUS effects . | REBUS effects . | ALBUS (powerfully altering internal working models) . |
|---|---|---|---|
| Depression | Behavioral activation; increased ability to imagine and experience positive outcomes | Interrupting depressogenic patterns of cognition and behavior (e.g. rumination) | Microdosing for behavioral activation Macrodosing for cognitive restructuring |
| Anxiety | Potential improvements through increased confidence, but possibly maladaptive effects due to greater vividness of negative imaginings | Reducing the grip of anxiety-provoking beliefs | Microdosing for increasing confidence, and possibly as an adjunct to exposure interventions Macrodosing for flooding and reconsolidation |
| Creativity | Both divergent and convergent creativity potentially elevated through enhanced associations and cognitive control | More divergent creativity through freer associations | Microdosing for either convergent or divergent creativity Macrodosing for divergent creativity |
| Autism spectrum | Potentially beneficial through reducing the gain on excessive prediction errors and increasing the gain on central integrative processes, but possibly contraindicated if accompanied by tendencies toward anxiety | Potentially beneficial for reducing overly rigid patterns and increasing cognitive flexibility, potentially insight | Microdosing for enhanced empathy and attenuated sensory sensitivity Macrodosing for breaking free of rigid patterns and promoting self/other awareness and insight |
| Schizophrenia spectrum | Likely contraindicated, unless condition is driven by functional disconnection, in which case some strengthening of beliefs could be beneficial | Potentially desirable for reducing some forms of delusions based on self-reinforcing beliefs; contraindicated if condition is driven by functional disconnection | Microdosing for enhancing executive functions Macrodosing as last-line intervention; possible protective effects for prodrome through enhancing integration, and possibly inoculation with respect to epistemic hygiene |
| Traumatic brain injury | Potentially protective by encouraging sustained cognitive engagement, preventing learned nonuse, and promoting neuroplasticity | Potentially useful for processing distress and maladaptive cognition and behavior patterns (e.g. cognitive avoidance and activity avoidance) | Microdosing for aiding recovery Macrodosing for breaking through maladaptive patterns to make room for new ones; may also be most beneficial for opening plasticity windows |
| Cognitive decline | Potentially beneficial for similar reasons to those described for traumatic brain injury | Potentially beneficial for similar reasons to those described for traumatic brain injury | Microdosing for prevention Macrodosing for condition management (and possibly prevention if avoidance contributes to cognitive reserve depletion) |
| Wakefulness disorders | Potentially highly beneficial by increasing consciousness level | Potentially beneficial if relaxed beliefs indirectly produce arousal through increased prediction errors | Microdosing for conditions such as narcolepsy Macrodosing as potentially beneficial for coma and persistent vegetative states |
| Addiction | Potentially contraindicated, unless microdosing provides an effective substitution for more addictive substances; increased abilities to visualize consequences/goals and greater connections to values could aid in resisting overly steep discounting of future utility | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as potential substitute for stimulants Macrodosing as potentially beneficial for all addictions |
| Personality disorders | Likely contraindicated as a standalone treatment, but potentially beneficial in conjunction with psychotherapy | Potentially beneficial via insight, unless psychedelic experiences promote spiritual bypassing or destabilize already weakened self-processes | Microdosing as adjunct to psychotherapy Macrodosing for updating maladaptive internal working models; potentially more effective with guided sessions |
| Post-traumatic stress disorder | Potentially contraindicated outside of exposure therapies due to risk of enhancing traumatic imaginings Possibly beneficial if other beliefs are allowed to more effectively compete with dominance from self-traumatizing internal models | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as adjunct for gradual exposure therapies Macrodosing for flooding and compassion-based protocols |
| Chronic pain | Likely highly variable across individuals, with some experiencing undesirable strengthening of pain-enhancing patterns of cognition, and others experiencing potentially beneficial reward-related analgesia (above and beyond anti-inflammatory properties associated with 5-HT2a receptors); possibly effective as adjunct to hypnosis-based interventions | Potentially beneficial for disrupting self-reinforcing patterns of pain-enhancing cognition; possibly temporarily harmful if reduced gating of prediction errors exacerbates pain sensations | Microdosing for reward-related analgesia and anti-inflammatory effects Macrodosing for enhancing self-compassion and acceptance |
| Terminal illness | Potentially helpful by strengthening access to sources of meaning from core values and transpersonal connection | Potentially beneficial by weakening schemas involving death anxiety | Microdosing for increased engagement with life Macrodosing for greater acceptance, connecting to higher meanings, and hopefully beneficial (and possibly transcendent) changes in worldview |
| Existential anxiety | Potentially helpful for similar reasons to those involved in overcoming distress from terminal illness | Potentially beneficial if connections to meaning are actively blocked by preexisting schemas | Microdosing for greater sense of agency, engagement with life, and connection to meanings Macrodosing as potentially beneficial for similar reasons to those involved with terminal illness |
| . | SEBUS effects . | REBUS effects . | ALBUS (powerfully altering internal working models) . |
|---|---|---|---|
| Depression | Behavioral activation; increased ability to imagine and experience positive outcomes | Interrupting depressogenic patterns of cognition and behavior (e.g. rumination) | Microdosing for behavioral activation Macrodosing for cognitive restructuring |
| Anxiety | Potential improvements through increased confidence, but possibly maladaptive effects due to greater vividness of negative imaginings | Reducing the grip of anxiety-provoking beliefs | Microdosing for increasing confidence, and possibly as an adjunct to exposure interventions Macrodosing for flooding and reconsolidation |
| Creativity | Both divergent and convergent creativity potentially elevated through enhanced associations and cognitive control | More divergent creativity through freer associations | Microdosing for either convergent or divergent creativity Macrodosing for divergent creativity |
| Autism spectrum | Potentially beneficial through reducing the gain on excessive prediction errors and increasing the gain on central integrative processes, but possibly contraindicated if accompanied by tendencies toward anxiety | Potentially beneficial for reducing overly rigid patterns and increasing cognitive flexibility, potentially insight | Microdosing for enhanced empathy and attenuated sensory sensitivity Macrodosing for breaking free of rigid patterns and promoting self/other awareness and insight |
| Schizophrenia spectrum | Likely contraindicated, unless condition is driven by functional disconnection, in which case some strengthening of beliefs could be beneficial | Potentially desirable for reducing some forms of delusions based on self-reinforcing beliefs; contraindicated if condition is driven by functional disconnection | Microdosing for enhancing executive functions Macrodosing as last-line intervention; possible protective effects for prodrome through enhancing integration, and possibly inoculation with respect to epistemic hygiene |
| Traumatic brain injury | Potentially protective by encouraging sustained cognitive engagement, preventing learned nonuse, and promoting neuroplasticity | Potentially useful for processing distress and maladaptive cognition and behavior patterns (e.g. cognitive avoidance and activity avoidance) | Microdosing for aiding recovery Macrodosing for breaking through maladaptive patterns to make room for new ones; may also be most beneficial for opening plasticity windows |
| Cognitive decline | Potentially beneficial for similar reasons to those described for traumatic brain injury | Potentially beneficial for similar reasons to those described for traumatic brain injury | Microdosing for prevention Macrodosing for condition management (and possibly prevention if avoidance contributes to cognitive reserve depletion) |
| Wakefulness disorders | Potentially highly beneficial by increasing consciousness level | Potentially beneficial if relaxed beliefs indirectly produce arousal through increased prediction errors | Microdosing for conditions such as narcolepsy Macrodosing as potentially beneficial for coma and persistent vegetative states |
| Addiction | Potentially contraindicated, unless microdosing provides an effective substitution for more addictive substances; increased abilities to visualize consequences/goals and greater connections to values could aid in resisting overly steep discounting of future utility | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as potential substitute for stimulants Macrodosing as potentially beneficial for all addictions |
| Personality disorders | Likely contraindicated as a standalone treatment, but potentially beneficial in conjunction with psychotherapy | Potentially beneficial via insight, unless psychedelic experiences promote spiritual bypassing or destabilize already weakened self-processes | Microdosing as adjunct to psychotherapy Macrodosing for updating maladaptive internal working models; potentially more effective with guided sessions |
| Post-traumatic stress disorder | Potentially contraindicated outside of exposure therapies due to risk of enhancing traumatic imaginings Possibly beneficial if other beliefs are allowed to more effectively compete with dominance from self-traumatizing internal models | Potentially beneficial by weakening overly strong self-reinforcing memories | Microdosing as adjunct for gradual exposure therapies Macrodosing for flooding and compassion-based protocols |
| Chronic pain | Likely highly variable across individuals, with some experiencing undesirable strengthening of pain-enhancing patterns of cognition, and others experiencing potentially beneficial reward-related analgesia (above and beyond anti-inflammatory properties associated with 5-HT2a receptors); possibly effective as adjunct to hypnosis-based interventions | Potentially beneficial for disrupting self-reinforcing patterns of pain-enhancing cognition; possibly temporarily harmful if reduced gating of prediction errors exacerbates pain sensations | Microdosing for reward-related analgesia and anti-inflammatory effects Macrodosing for enhancing self-compassion and acceptance |
| Terminal illness | Potentially helpful by strengthening access to sources of meaning from core values and transpersonal connection | Potentially beneficial by weakening schemas involving death anxiety | Microdosing for increased engagement with life Macrodosing for greater acceptance, connecting to higher meanings, and hopefully beneficial (and possibly transcendent) changes in worldview |
| Existential anxiety | Potentially helpful for similar reasons to those involved in overcoming distress from terminal illness | Potentially beneficial if connections to meaning are actively blocked by preexisting schemas | Microdosing for greater sense of agency, engagement with life, and connection to meanings Macrodosing as potentially beneficial for similar reasons to those involved with terminal illness |
This table is neither meant to be exhaustive nor definitive.
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