Part 1: Psychedelics and dissociative drugs
This article was written by our trainer Maria Vittoria Zulli
Psychedelics (LSD, Psilocybin, Ayahuasca)
Psychedelic drugs have profound effects on human perception, cognition and emotions, which induce an altered state of consciousness (Studerus et al., 2010). These effects are mainly mediated by the drug’s ability to bind to serotonin receptors in the brain, modulating the activity of key circuits involved in perception and cognition (Halberstadt, 2015). One of the key mechanisms underlying the unique and rapid effects of psychedelics is their ability to dramatically alter the brain's functional connectivity states, as observed through functional neuroimaging methods such as fMRI and EEG. For example, an fMRI study showed that Psilocybin, a common psychedelic, reduces neuronal activity and functional connectivity in brain regions involved in cognition, perception, and mood, such as the anterior and posterior cingulate cortices (Carhart-Harris et al., 2014). Other studies have demonstrated that psychedelics, such as Psilocybin and Ayahuasca, can reduce activity in the brain’s default mode network and alter functional connectivity between brain regions (Smigielski et al., 2019; Palhano-Fontes et al., 2015).
Repeated use of psychedelic drugs can have long-term effects, including the risk of experiencing flashbacks of the drug experience after its effects have worn off or developing hallucinogen persisting perception disorder (HPPD). Although the occurrence of either is rare, it can happen even after a single exposure to the drug (U.S Department of Health and Human Services, 2022). The altered states of consciousness induced by psychedelics share common features with psychotic states, such as the disorganisation of thought and perception. Still, there is no conclusive evidence linking long-term psychedelic use to persistent psychosis symptoms (Cormier, 2015).
Psychedelics and EEG changes
Numerous studies have investigated the effects of psychedelics on EEG. Studies using serotonergic psychedelics in humans consistently show a decrease in spectral power across a broad range of frequencies (delta to gamma), with the most pronounced decrease in the alpha band (8-12 Hz). Additionally, there is a decrease in functional connectivity and network integrity (Riba et al., 2004; Stuckey et al., 2005; Kometer et al., 2015; Pallavicini et al., 2019; Timmermann et al., 2019). Decreased alpha power is a consistent finding in neuroimaging research with psychedelics (Carhart-Harris et al., 2016). Alpha is the most prominent rhythm of the resting brain (Başar & Güntekin, 2009), linked to high-level psychological functioning (Klimesch 2012), top-down processing (Mayer et al., 2016), and related feedback connectivity (van Kerkoerle et al., 2014), all of which are disrupted under serotonergic psychedelics (Alonso et al., 2015; Timmermann et al., 2018). Increases in higher frequencies, such as gamma oscillations (30Hz and above), have also been described (Riba et al., 2002; Schenberg et al., 2015); however, interpreting the effects is challenging due to contamination from increased muscle tension.
When looking at the effects of Ayahuasca on EEG, Riba and colleagues found decreased power density in the alpha, delta, theta and beta frequency bands, with the most significant decreases observed over the temporal-parietal-occipital junction for delta, alpha and beta bands, while theta power was reduced in the temporomedial cortex and in front-medial regions (Riba et al., 2004). These broadband decreases in cortical oscillatory power have also been observed in studies with psilocybin (Muthukumaraswamy et al., 2013).
Studies investigating the effects of LSD on EEG changes have shown decreased visual cortex alpha power, which predicted the magnitude of visual hallucinations, and reduced Default Mode Network Integrity, a group of brain regions that are active during introspection and support internal mental simulations (Buckner, 2013). Furthermore, LSD has also been found to decrease delta and alpha power in the posterior cingulate cortex correlating with profound changes in consciousness (Carhart-Harris et al., 2016).
Another study looking at LSD and psilocybin (using MEG) found that these drugs cause widespread and broadband power reductions in occipital, parietal and frontal regions in the low alpha and theta bands, as well as decreases in low beta activity (Pallavicini et al., 2019).
Interestingly, a study conducted on rats revealed EEG activity changes similar to those observed in humans who use psychedelics. These changes included a global decrease/desynchronisation of EEG activity and disconnection within 1-40Hz, as well as a decrease in global connectivity (Vejmola et al., 2021).
Ecstasy, also known as MDMA, is a psychostimulant drug that can produce a sense of euphoria and increase sociability. However, it is also neurotoxic, particularly to the serotonin neurotransmitter system, which plays a crucial role in regulating mood, appetite, and sleep (Capela et al., 2007). The use of MDMA can lead to damage of serotonin neurons in the brain, contributing to the cognitive and emotional problems associated with the drug. Various medical and psychiatric problems have been linked to MDMA use, including cognitive impairments such as deficits in memory and attention (Reneman et al., 2006). Thus, while ecstasy may produce pleasurable effects in the short term, it can have serious long-term consequences on brain function and mental health.
Studies have shown that the use of ecstasy can cause changes in EEG patterns in humans. One study found that polydrug users who consumed ecstasy showed increases in the absolute power of beta, low alpha and theta activities (Adamaszek et al., 2010). The study also observed a dose-dependent increase around 5 and 20 Hz in subjects with medium to high ecstasy use. Similarly, another study conducted by Gamma et al. (2000) found global and localised increases of EEG alpha and beta frequency activity in regular ecstasy users compared to healthy controls. However, both studies were conducted on polydrug users, which presents methodological limitations. It is worth noting that pure ecstasy users are uncommon, and investigations of isolated ecstasy effects have been unsuccessful and do not appear feasible (Zakzanis et al., 2001)
Dissociative hallucinogens such as Ketamine and Phencyclidine (PCP) can significantly alter a person’s experience of reality. These drugs can cause visual and auditory hallucinations, sensory distortion, and intense emotional reactions or experiences. Ketamine and PCP exert their dissociative and hallucinogenic effects by disrupting the action of the brain chemical glutamate at NMDA receptors (Morgan, et al., 2012). Glutamate plays a major role in cognitive function, learning, memory and emotion regulation. Glutamate dysregulation is implicated in various neuropsychiatric disorders, including schizophrenia and depression (Marsman et al., 2013).
PCP and ketamine can induce psychotic symptoms and neurocognitive deficits similar to those seen in schizophrenia by blocking neurotransmission at NMDA glutamate receptors (Javitt, 2007). In addition, PCP and ketamine have been shown to exacerbate symptoms in schizophrenics and reactivate symptoms in those in remission (Jentsch et al., 1999).
Ketamine and EEG changes
Ketamine is commonly used as a dissociative anaesthetic, but it also has additional properties such as analgesia, amnesia, and fast-acting antidepressant effects (Berman et al., 2000; Rowland 2005; Aroni et al., 2009). At low doses, ketamine can induce a dissociative state characterised by altered sensory perception, hallucinations, and analgesia. However, at higher doses, it can produce unconsciousness appropriate for general anaesthesia.
Chronic ketamine abuse has been associated with long-term cognitive impairment, mood disorders, and psychotic and dissociative symptoms (Strous et al., 2022). Ketamine consumption also leads to neurological changes in regions of the prefrontal cortex that are involved in working memory and executive functions (Narendran et al., 2005; Morgan & Curran, 2006).
Research suggests that ketamine induces changes in brain connectivity that may underlie its various effects on analgesia, psychedelic experiences, and other side effects. In healthy individuals who were administered ketamine, resting-state fMRI data revealed alterations in connectivity similar to those observed in the early stages of schizophrenia (Fleming et al., 2019). Furthermore, studies have shown that ketamine modifies connectivity in brain regions implicated in endogenous pain modulation (Niesters et al., 2012).
While the effects of ketamine on EEG have been extensively researched, some studies have primarily focused on anaesthesia. Research on ketamine-induced unconsciousness has discovered a gamma burst pattern of alternating slow delta (0.1-4 Hz) and gamma (27-40 Hz) brainwaves, along with increased theta waves (4-8 Hz) and decreased alpha and beta (10-24 Hz) brainwaves (Akeju et al., 2016; Bojak et al., 2013).
Some discrepancies exist in the literature. Some studies suggest that ketamine reduces frontal-parietal network connectivity in the alpha bandwidth and increases gamma power, which may explain ketamine-induced unconsciousness (Blain-Moraes et al., 2014; Lee et al., 2013). However, other studies using lower doses of ketamine have also observed reductions in frontal-parietal connectivity of alpha in awake patients, suggesting that the reductions in connectivity may not be solely associated with loss of consciousness (Muthukumaraswamy et al., 2015). Further research is necessary to understand the underlying neurophysiological processes associated with ketamine-induced states.
PCP-induced EEG changes
Phencyclidine (PCP) is a dissociative anaesthetic drug that is primarily used recreationally due to its mind-altering effects, which can result in an altered perception of reality, disordered thinking, euphoria, agitation, and aggression.
Animal studies have shown that PCP produces a pattern of metabolic and neurochemical changes in the brain that resemble those observed in individuals with schizophrenia (Morris et al., 2005). PCP can induce psychosis by affecting the function of the PFC (Jodo, 2013), a crucial brain region implicated in schizophrenia and responsible for attention, focus, inhibition of behaviour, and other functions (Weinberger et al., 1986). Long-term use of PCP can result in PFC neuronal damage, leading to attentional problems, lack of impulse control, aggression and violent behaviours.
Moreover, PCP can also alter dopamine signalling in the brain, which may contribute to the development of psychotic symptoms such as hallucinations and delusions, similar to what is observed in schizophrenia. The relationship between PCP, glutamate, dopamine and schizophrenia is complex, and further research is needed to fully comprehend the underlying mechanisms. However, it is evident that disruption in glutamate signalling can lead to altered dopamine signalling, which may contribute to the manifestation of psychotic symptoms associated with schizophrenia (McCutcheon et al., 2020)
PCP also affects other neurotransmitters, such as endorphins, involved in the suppression of pain and reduction of stress, which may account for PCP’s anaesthetic effects (Bey & Patel, 2007).
Although PCP has been shown to have an impact on EEG, only a limited number of studies have been conducted, and most of them have used animal studies. One study using rats found that PCP injection at a dose of 2 mg/kg resulted in an increase in the power of theta waves (6-8 Hz), accompanied by behavioural arousal and hyperactivity. Higher doses of PCP (4 and 8 mg/kg) induced an increase in delta power (1-3 Hz) with limited locomotion, ataxia and stereotypy (Mattia et al., 1986). Theta and Delta waves are associated with drowsiness and slow-wave sleep. Another study conducted in monkeys showed that administration of PCP resulted in the inhibition of delta waves (0.6-0.8 Hz) in the parietal lobe and theta waves (4-5) in the occipital lobes and hippocampus, with excitatory periods of theta enhancement during behavioural arousal (Matsuzaki & Dowling, 1985). The limited research on the effects of PCP on EEG in humans is primarily due to ethical concerns and potential harm to participants. Although there have been some animal studies on this topic, it remains an understudied area in human research compared to other aspects of PCP pharmacology and schizophrenia research.
Full list of references for this article can be found here