One mechanism proposed to underlie the psychedelic state is the alteration of information processing within cortico-striato-thalamo-cortical feedback loops. Studies have shown that LSD increases functional connectivity between the thalamus and sensory-somatomotor cortical regions, strengthening specific connections between these areas.
LSD also decreases connectivity from the thalamus to the temporal cortex and increases connectivity to the posterior cingulate cortex. Similarly, psilocybin and LSD have been found to increase interaction between sensory and somatomotor brain networks while decreasing communication among associative brain regions, including the Default Mode Network. These findings suggest that psychedelics enhance the processing of sensory information while reducing the integration capacity of associative brain networks.
Psilocybin decreases connectivity between the claustrum and the auditory network and the Default Mode Network, while increasing connectivity with the frontoparietal control network. Additionally, LSD has been found to increase connectivity between the amygdala and the frontal cortex, which is associated with positive mood.
While neuroimaging studies on psychedelics in clinical populations are limited, some insights have been gained. In patients with major depressive disorder (MDD), treatment response to psilocybin has been associated with changes in connectivity between the prefrontal cortex (PFC) and other brain regions. Decreased amygdala reactivity and increased amygdala-PFC connectivity have been linked to positive mood in healthy individuals under the influence of psychedelics.
However, patients with MDD showed increased amygdala reactivity and reduced amygdala-PFC connectivity in response to fearful faces after psilocybin administration, which was unexpected. It is possible that psilocybin facilitated the processing of negative emotions in these patients, leading to increased amygdala reactivity.
Psychedelics, such as psilocybin, LSD, and DMT, have shown promise in the treatment of various mental health conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD). Understanding the neurobiological mechanisms underlying these therapeutic effects is crucial for optimizing their use in clinical settings.
One hypothesis suggests that psychedelics promote neuroplasticity and enhance the ability of the brain to reorganize itself. Studies have shown that psychedelics increase the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), which play a critical role in promoting the growth and maintenance of neurons. Increased neuroplasticity may facilitate the rewiring of neural circuits and the formation of new connections, allowing for novel insights and perspectives.
Moreover, psychedelics have been found to modulate serotonin receptors, particularly the serotonin 2A receptor (5-HT2A). Activation of 5-HT2A receptors leads to a cascade of downstream effects, including increased glutamate release, alterations in cortical excitability, and changes in the balance between inhibitory and excitatory neurotransmission. These changes in serotonin signaling and glutamate release likely contribute to the unique subjective experiences induced by psychedelics.
Another important aspect of psychedelics’ effects on the brain is their impact on the Default Mode Network (DMN). The DMN is a network of brain regions that is active during introspection, self-reflection, and mind wandering. Abnormalities in the DMN have been observed in various psychiatric disorders. Psychedelics have been found to reduce the integrity of the DMN, leading to a decrease in the coherence and connectivity among its constituent brain regions. This disruption of the DMN may contribute to the dissolution of the self and the profound alterations in perception and consciousness experienced during a psychedelic trip.
Furthermore, psychedelics have been shown to promote emotional processing and facilitate the retrieval of repressed or emotionally charged memories. This can lead to a heightened emotional state during the acute effects of the drug, which may be followed by a subsequent integration period where individuals can reflect on and make sense of their experiences. The increased emotional processing and memory retrieval facilitated by psychedelics may contribute to their therapeutic potential, particularly in the context of trauma-related disorders.
Psychedelics, such as psilocybin (magic mushrooms), LSD, and ayahuasca, have gained considerable attention in recent years for their potential therapeutic benefits in treating mental health conditions like depression, anxiety, and PTSD.
However, in addition to their clinical applications, there is a growing trend of individuals using psychedelics in a naturalistic or non-clinical setting for personal growth, self-exploration, and spiritual experiences.
Naturalistic use of psychedelics refers to the ingestion of these substances outside of controlled research environments and without the guidance of a trained therapist. People who engage in naturalistic psychedelic use often seek profound and transformative experiences that can lead to insights, personal development, and enhanced well-being.
Reasons for Naturalistic Use:
- Personal Growth and Self-Exploration: Many individuals turn to psychedelics as a means of gaining deeper insights into their own thoughts, emotions, and behaviors. These substances are believed to induce altered states of consciousness that can promote self-reflection and self-discovery.
- Spiritual and Mystical Experiences: Psychedelics have been used for centuries in various cultures for their potential to facilitate mystical or spiritual experiences. Some people use psychedelics as a way to connect with a higher power, explore existential questions, or experience a sense of unity and interconnectedness.
- Creativity and Inspiration: Psychedelics have long been associated with enhancing creativity and providing artistic inspiration. Many artists, musicians, writers, and other creative individuals have reported using psychedelics to access new perspectives, overcome creative blocks, and tap into their creative potential.
- Healing and Emotional Well-being: Some individuals turn to psychedelics as a means of addressing emotional wounds, traumas, or unresolved issues. Psychedelic experiences can sometimes bring buried emotions to the surface, allowing individuals to process and integrate them in a transformative way.
Challenges and Considerations: While naturalistic use of psychedelics can be a positive and meaningful experience for many individuals, there are important considerations and potential risks involved:
- Safety and Legality: Psychedelics are classified as illegal substances in many countries. Obtaining and using them outside of legal frameworks carries legal risks. Ensuring the purity and quality of substances obtained from illicit sources can also be challenging, leading to potential health risks.
- Set and Setting: The mindset and environment in which psychedelics are consumed can greatly influence the experience. It is crucial to create a safe, supportive, and comfortable setting, ideally with trusted individuals who can provide emotional support if needed.
- Psychological Vulnerability: Psychedelics can bring forth intense emotions and experiences. Individuals with a history of mental health conditions, such as psychosis or severe anxiety, may be more vulnerable to adverse effects and should exercise caution.
- Integration: The experiences induced by psychedelics can be profound and complex. Integration, the process of making sense of and integrating the insights gained during the psychedelic experience into everyday life, is crucial. Having support systems in place, such as therapy or integration circles, can aid in effectively integrating these experiences.
- Personal Responsibility: Engaging in naturalistic psychedelic use requires a sense of personal responsibility and informed decision-making. It is important to educate oneself about the substances, potential risks, and harm reduction strategies. Open and honest communication with healthcare professionals and trusted individuals can provide valuable guidance and support.
Here’s a list of various substances with psychedelic effects, along with a description of their effects:
- Lysergic Acid Diethylamide (LSD): LSD is a potent hallucinogenic substance. Its effects include:
- Visual hallucinations, such as geometric patterns, color distortions, and enhanced perception of light.
- Altered sense of time, with minutes feeling like hours or hours feeling like minutes.
- Ego dissolution and a sense of interconnectedness.
- Emotional changes, ranging from euphoria to anxiety.
- Cognitive effects, such as enhanced creativity and expanded thinking.
- Physical effects like dilated pupils, increased heart rate, and altered appetite.
- Psilocybin Mushrooms: Psilocybin is a naturally occurring compound found in certain mushrooms. The effects of psilocybin mushrooms include:
- Visual hallucinations, including geometric patterns and distorted shapes.
- Mood elevation, with feelings of joy, love, and connectedness.
- Altered perception of time and space.
- Spiritual and mystical experiences.
- Increased introspection and self-reflection.
- Possible nausea and changes in body temperature and blood pressure.
- Dimethyltryptamine (DMT): DMT is a powerful hallucinogenic compound found in various plants. Its effects include:
- Intense visual hallucinations, often described as vivid and immersive, including encounters with entities and otherworldly landscapes.
- Altered sense of self and reality.
- Ego dissolution and a feeling of unity with the universe.
- Profound spiritual and mystical experiences.
- Rapid onset and short duration of effects (often referred to as a “breakthrough” experience).
- Increased heart rate and blood pressure.
- Mescaline (Peyote and San Pedro Cactus): Mescaline is a naturally occurring psychedelic found in certain cacti. Its effects include:
- Visual hallucinations, such as enhanced colors, patterns, and shapes.
- Altered perception of the body and the environment.
- Heightened sensory experiences.
- Spiritual and mystical experiences.
- Emotional shifts, ranging from euphoria to anxiety.
- Changes in thinking patterns and introspection.
- Ayahuasca: Ayahuasca is a traditional plant-based brew containing DMT and other psychoactive compounds. Its effects include:
- Profound visual hallucinations, often accompanied by a strong sense of symbolism.
- Emotional catharsis and release of repressed emotions.
- Intense introspection and self-reflection.
- Spiritual and transformative experiences.
- Purging effects (vomiting or diarrhea) as part of the cleansing process.
- Increased heart rate and blood pressure.
- 2C-B: 2C-B is a synthetic psychedelic compound. Its effects include:
- Visual hallucinations, ranging from mild distortions to intense visuals.
- Euphoria and increased sensory perception.
- Enhanced empathy and sociability.
- Mild stimulant-like effects, including increased energy and arousal.
- Altered sense of time and space.
- Potential changes in body temperature and blood pressure.
- Ketamine: Ketamine is a dissociative anesthetic that can induce psychedelic effects at higher doses. Its effects include:
- Dissociation from the body and surroundings.
- Visual and auditory hallucinations, often described as dream-like or otherworldly.
- Analgesic properties and potential pain relief.
- Altered perception of time and space.
- Possible sedation and relaxation.
- Potential dissociative aftereffects and temporary memory impairment.
- Salvia divinorum: Salvia divinorum is a plant that contains the psychoactive compound salvinorin A. Its effects include:
- Intense and rapid-onset hallucinations, often described as dream-like or surreal.
- Altered perception of the body and environment.
- Distorted sense of time and space.
- Euphoria or dysphoria, depending on the individual and the dosage.
- Potential loss of motor control and coordination.
- Short duration of effects, typically lasting only a few minutes.
- Ibogaine: Ibogaine is a psychoactive alkaloid found in the iboga plant. Its effects include:
- Deep introspection and self-reflection.
- Visual and auditory hallucinations, often involving personal memories or spiritual experiences.
- Potential emotional and psychological healing.
- Detoxification and potential reduction of withdrawal symptoms in substance dependence.
- Stimulant effects at lower doses and sedative effects at higher doses.
- Potential cardiovascular effects and risk of adverse reactions.
- 5-MeO-DMT: 5-MeO-DMT is a potent psychedelic compound found in various plants and toad secretions. Its effects include:
- Profound and intense ego dissolution and unity with the universe.
- Rapid-onset and short duration of effects.
- Overwhelming sensory and visual experiences, often described as “ego death.”
- Enhanced perception and altered sense of time.
- Potential for spiritual and transformative experiences.
- Increased heart rate and blood pressure.
- DOM (STP): DOM is a synthetic psychedelic compound known for its long duration of effects. Its effects include:
- Visual hallucinations, including enhanced colors and patterns.
- Altered perception of time and space.
- Increased sensory perception and heightened emotions.
- Stimulation and potential increase in energy levels.
- Potential for intense and prolonged trips lasting up to 24 hours.
- Adverse physical effects such as vasoconstriction and increased body temperature.
- DOB: DOB is a synthetic psychedelic compound similar to DOM. Its effects include:
- Visual and auditory hallucinations, ranging from mild distortions to intense visuals.
- Altered perception of time and space.
- Increased energy and stimulation.
- Enhanced sensory experiences.
- Potential for a prolonged duration of effects.
- Adverse physical effects such as vasoconstriction and increased heart rate.
- DXM: DXM (dextromethorphan) is a cough suppressant that can produce dissociative and psychedelic effects at higher doses. Its effects include:
- Dissociation from the body and surroundings.
- Altered perception of time, space, and self.
- Visual and auditory hallucinations, often described as dream-like or otherworldly.
- Potential for euphoria and emotional changes.
- Variable effects depending on the dosage and individual metabolism.
- Potential for adverse effects when combined with other substances.
Here is a detailed description of how psilocybin works on the brain:
- Serotonin 2A Receptor Activation: Psilocybin, the active compound in magic mushrooms, primarily interacts with serotonin 2A receptors (5-HT2A) in the brain. Psilocybin is metabolized into psilocin, which acts as a partial agonist at these receptors. Activation of 5-HT2A receptors leads to a cascade of effects that contribute to the psychedelic experience.
- Disruption of Default Mode Network (DMN): The DMN is a network of brain regions that is active during introspection and self-referential thinking. Psilocybin has been shown to disrupt the activity and connectivity within the DMN. This disruption is thought to contribute to the dissolution of the self, altered sense of identity, and ego dissolution experienced during a psychedelic trip.
- Increased Cortical Excitation: Psilocybin increases cortical excitability by stimulating glutamate release, the primary excitatory neurotransmitter in the brain. This increased excitability may lead to enhanced sensory perception, heightened emotions, and altered thought patterns.
- Altered Communication between Brain Regions: Psilocybin alters communication between different brain regions. It increases the connectivity between sensory and somatomotor brain networks while decreasing connectivity among associative brain regions. This shift in connectivity patterns may contribute to the distortion of sensory perception, synesthesia (cross-sensory experiences), and the blending of different aspects of experience.
- Neuroplasticity and Synaptic Remodeling: Psilocybin has been shown to increase the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF). These factors play a crucial role in promoting neuroplasticity, the brain’s ability to reorganize and form new connections. Increased neuroplasticity may underlie the long-lasting effects and potential therapeutic benefits of psilocybin.
- Emotional Processing and Memory Retrieval: Psilocybin can enhance emotional processing and facilitate the retrieval of repressed or emotionally charged memories. This can lead to intense emotional experiences during the acute effects of the drug. Subsequently, during the integration period after the trip, individuals may have an opportunity to reflect on and gain insights from these emotional experiences.
- Reduction of Amygdala Reactivity: The amygdala is a brain region involved in processing emotions, particularly fear and anxiety. Psilocybin has been found to reduce amygdala reactivity, potentially leading to a reduction in fear responses. This reduction in amygdala reactivity may be associated with the therapeutic effects of psilocybin in conditions such as anxiety disorders and post-traumatic stress disorder (PTSD).
- Increased Connectivity in Frontoparietal Control Network: Psilocybin has been shown to increase connectivity in the frontoparietal control network, which is involved in cognitive control, attention, and decision-making. This increased connectivity may contribute to the heightened introspection, self-reflection, and enhanced cognitive flexibility often reported during a psychedelic experience.
- Thalamic Gating: Psilocybin is thought to affect the thalamus, a brain region that acts as a gateway for sensory information. It has been proposed that psilocybin reduces thalamic gating, allowing an increased flow of sensory information to reach the cortex. This may contribute to the amplification of sensory experiences and the vividness of perception reported during a psychedelic trip.
- Entropy and Increased Brain Complexity: Psilocybin has been found to increase the entropy and complexity of brain activity. Entropy refers to the measure of randomness or disorder within a system, while complexity refers to the richness and diversity of connections and interactions. The increased entropy and complexity may underlie the expansion of consciousness, the emergence of novel thoughts and ideas, and the heightened creative and imaginative processes experienced during a trip.
- Modulation of Brain Waves: Psilocybin has been shown to modulate brain wave activity. It reduces alpha oscillations, particularly over posterior parieto-occipital brain areas. This reduction in alpha oscillations may increase the excitability of the visual pathway, leading to visual hallucinations and altered visual perception. Psilocybin also affects other brain wave frequencies, including theta and gamma, which are associated with cognitive processes and consciousness.
- Neurogenesis: There is evidence to suggest that psilocybin may promote neurogenesis, the generation of new neurons in the brain. Animal studies have shown that psilocybin increases neurogenesis in the hippocampus, a region involved in learning, memory, and emotional regulation. This potential neurogenic effect may contribute to the long-term neuroplastic changes and antidepressant effects associated with psilocybin.
- Altered Sense of Time and Space: Psilocybin can distort the perception of time and space. The subjective experience of time may appear to slow down or speed up, and the boundaries between the self and the external world may become blurred. This alteration in temporal and spatial perception is thought to arise from the disruption of neural networks involved in temporal processing and the integration of sensory information.
- Psychoanalytic Effects: Psilocybin can induce introspection, self-reflection, and insight into one’s thoughts, emotions, and behaviors. This introspective process can facilitate the exploration of deep-seated psychological issues and promote psychological healing. The experience may uncover repressed memories, unresolved conflicts, and provide individuals with new perspectives on their lives, leading to personal growth and therapeutic breakthroughs.
- Integration of Brain Networks: Psilocybin promotes the integration of brain networks that are typically segregated and operate independently. This increased integration may foster a sense of unity, interconnectedness, and a dissolution of boundaries between self and others. It has been proposed that the enhanced connectivity and integration of brain networks contribute to the mystical, spiritual, and transcendent experiences reported during a psychedelic journey.
reference link :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880300/
https://www.tandfonline.com/doi/full/10.1080/02791072.2023.2201263
