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Ibogaine Therapy in Chemical Dependency and Posttraumatic Stress Disorder: A Hypothesis Involving the Fractal Nature of Fetal REM Sleep and Interhemispheric Reintegration. 
C.M. Anderson, Ph D. Consolidated Department of Psychiatry, Harvard Medical School, and the Developmental Biopsychiatry Research Program, McLean Hospital, Belmont, MA 02178, USA. (carl_anderson@hms.harvard.edu) (an expanded version of the published article) 1/f Fractal Patterns in Time: The Common Ground of REM Sleep, Orienting and Psychedelic States The Fractal Geometry of Time in Neurobiology and Fetal REM sleep. Psychedelic Drug Induced Fractal Clustering in Serotonergic Network Output Patterns The Fractal Structure of REM Sleep in Fetal Sheep The Puzzle of REM Sleep in Sickness and in Heath: A Common Fractal Thread? Vertical Fractal Clusting: Insights into Developmental Stress, Trauma and PTSD. Emotional Memory, the Amygdala and Tripping in Fractal Time: Going Back to the Womb with Ibogaine " Banzie (the members of the Bwiti, properly, "those of the chapel") also say that eboga enables a man or woman to return to infancy and to birth - to the life in the womb....by returning initiates to the uterine condition, a condition in any case very close to life in the land of the dead [and so] restores them to their own integrity - their pristine conditions." -From Bwiti: an Ethnography of the Religious Imagination in Africa. James W. Fernandez, Princeton University Press, 1982, p . 491.
Inspired first by a synchronistic meeting with Dr. Debora Mash and Dr. Julie K. Staley, then by enigmatic descriptions of Bwiti lore, I have developed a hypothesis supporting the use of ibogaine, as well as other analogs or compounds with oneiric properties for the treatment of chemical dependency and posttraumatic stress disorder (PTSD). In short, ibogaine interacts with many neurotransmitter systems to drive amygdaloid-brainstem dynamics into a critical oneiric state, with fractal time patterns of phasic events similar to those existing during fetal rapid eye movement (REM) or Active sleep1. In effect, ibogaine pharmacodynamically destabilizes the functional connectivity of the brainstem and its habitual interactions with bihemispheric temporal lobe structures such as the amygdala, creating a functional state of plasticity in these areas which facilitates the reintegration of traumatic memories by altering psychopathological interhemispheric dynamics, ultimately dissipating addiction-related behavioral patterns. This psychotherapeutic oneiric state is similar to the complex behavioral states of REM sleep and attentional orienting in that they all share the signature of the self-organized critcal state, 1/f (one-over-f) patterns of activity involving many levels of the nervous system from the subcellular to the behavioral. Observed similarities between the neurophysiology of the REM state and that induced by selective psychedelic drugs such as LSD or psilocybin further support this hypothesis as does the observation that REM sleep, which is disrupted by drug abuse and traumatic experiences (1-5), has been shown to be essential for emotional regulation, learning and memory consolidation. Recent findings by many researchers, including the author, that stress or abuse in early life induces abnormal hemispheric functional asymmetries, disrupting REM sleep and predisposing patients to addictive and self-defeating behaviors resulting from impaired interhemispheric integration (6-11), support this new view of the psychobiology and treatment of addiction. How it all got started(Top) I met Dr. Debra Mash and Dr. Julie Staley in 1994 while I was working at Florida Atlantic University on my Ph.D dissertation which involved using fractal geometry to study the structure of REM sleep in fetal animals and its disruption by early stress. The occasion was a guest lecture given at the University of Miami by my mentor at FAU, Dr. Arnold Mandel, a pioneer in the application of chaos and nonlinear dynamics to psychiatry and neuropharmacology (12-17). Before the talk, Dr. Mash had taken me and others to lunch. There, during the rich conversation that ensued, Dr. Stanley spoke of evidence for the oneiric [dream inducing] properties of ibogaine, and it suddenly became clear to me that this might be related to the fractal patterns of REM sleep that I was investigating. After completing my dissertation in 1995, I began working on the effects of early sexual or verbal abuse in young adults, and continued my work on the effects of early deprivation with Dr. Martin Teicher and Dr. Friedric Schiffer at Mclean Hosptial (6, 9, 18, 19). Previous work by Dr. Schiffer and Dr. Teicher has demonstrated the profound and persistent neural and psychological changes induced by early trauma in EEG evidence of asymmetric hemispheric activation during the recall of past trauma (10). Further, abnormal hemispheric EEG coherence and reductions in the size of the corpus callosum were observed by Dr. Teicher and others with analysis of MRI images from abused and neglected children treated at McLean Hospital (11). Based on his clinical experience and the seminal work of Roger Sperry (20), Dr. Schiffer has proposed, that we all have, in fact, two minds or personalities, one in each hemisphere (21, 22). Using a new therapeutic technique called lateral visual field stimulation (LVFS), he has observed clinically a dramatic manifestation of disparate dual personalities in subjects who have suffered from abuse or PTSD during their lives. In effect, Dr. Schiffer proposes that our two hemispheres are like joined minds, mental Siamese twins, who learn in early life to function harmoniously sharing their unique specializations. This harmony is fragmented by abuse or trauma, which unbalances the twins and leads to a unending pathological struggles of dominance resulting in a wide range of personality disorders (22). For example, one twin, the right in many cases retains the abuse memory and as a result is less mature, and will take control in times of stress or anger, sabotaging the good efforts of the more mature side. This replaces the Freudian concept of the unconscious with Sperry's findings of two minds. Interhemispheric struggles, primary a result of child abuse, may be the fundamental psychological root of drug addiction. In a seminal chapter, entitled "The euphorohallucinogens", Mandell and Geyer (14) described how normal dual hemispheric organization may be particularly relevant to conceptualizing the neurobiological basis of psychedelic states:
&qu ot;It seems clear that the lateral specialization of the human cerebral cortex provides two distinct and complementary modes of consciousness and that they function more or less in concert with one another. By virtue of its focal organization and sequential processing, the dominant (usually the left ) side is best suited for verbal, mathematical, and analytic thought, whereas spatial orientation, artistic talent, visuoconstructive ability, and abstraction of part-whole relationships may well depend on the more diffuse organization that usually characterizes the right hemisphere. The startling perceptual experiences produced by hallucinogenic drugs may be more comprehensible in light of the capacity of the nondominant hemisphere for simultaneous integration of information. The heteromodal influx of perceptions produced by increased attentiveness and sensitization to sensory stimuli may overwhelm the systematic sequential processing of the language hemisphere and invoke the analogical integrative mode of the right hemisphere to consolidate the perceptual flood. However, with particular doses of hallucinogenic drugs, many subjects experience mind trips, bursts of ecstatic and sequentially logical thoughts, or the insight accompanying discovery (p. 592)." ;
Further, they anticipated the far reaching implications of interhemispheric warfare in psychotherapeutic approaches to the treatment of psychopathology:
"Supportive psychotherapy, often an alliance between the therapist and only one of the patient's hemispheres based on a common enemy--doctor and patient agree that the mother is the villain--makes one side dominant, eliminating conflict by splitting, just as tricyclics [antidepressants] exaggerate the influence of one lobe (p. 597)."
In contrast, Dr. Schiffer's LVFS-based psychotherapy may allow clinicians to bring the psychopathological struggles between the twin hemispheres to the patient's full awareness, facilitating a degree of resolution and harmony. Within this unique and creative perspective of abnormal relationships between the two hemispheres or minds, LVFS therapy can provide a fundamentally new understanding of traditional psychotherapeutic techniques, as well as controversial and groundbreaking techniques such as eye movement desensitization reprocessing [EMDR: (23)] and transcranial magnetic stimulation [TMS:(24)]. In addition, this view can inform traditional and innovative psychopharmacological approaches (e.g., the psychotherapeutic use of psychedelics). After researching the ethnological literature and many anecdotal accounts of addicts over the last four years, I believe that ibogaine, when used in a proper long-term supportive social and psychotherapeutic context, can end drug addictions and possibly the underlying PTSD, by promoting, especially during the cognitive evaluation phase, balanced hemispheric interactions. Just as The Fang adopted the use of eboga to promote social and religious harmony during colonialism-induced social and cultural fragmentation (25), our world society which is experiencing a similarly deep social fragmentation, accelerated by the soulless march of materialism and concurrent environmental degradation, and marked by escalating drug addiction and suicidal behavior among our youth, may benefit from judicious use of the ibogaine or related agents. Ibogaine, possibly in combination with hemispheric reintegration techniques, may potentially free the minds of many individuals (addicts, rape victims, violent criminals, victims of child abuse, war or natural disasters) suffering from the debilitating emotional disregulation resulting from hemispheric disharmony. Publishing this paper in MAPS is an attempt to present this hypothesis in the context of new perspectives on the role of fractal patterns and abnormal hemispheric interactions in brain function to an "open minded" or "hemispherically-balanced2" audience for wider constructive criticism. In the following sections I will attempt to give the reader a useful introduction to fractal concepts and why they provide an essential point of view for understanding brain/mind. Fascinating connections among REM sleep, attentional and psychedelic states will be established using fractal concepts leading to a description of ibogaine therapy in the context of the involvement of cortical-amygdaloid-brainstem loops in hemispheric disharmony. Neurophysiological Similarities Between REM Sleep, Orienting and Psychedelic States: Implications for Oneiric Drugs.(Top) In 1979 Drs. Barry Jacobs and Michael Trulson published a speculative article in the then newly formed journal Trends In The Neurosciences entitled "Dreams, hallucinations, and psychosis - the serotonin connection," suggesting a connection between hallucinogenic drugs, dreams and amphetamine psychosis (26). Previously, they had developed an animal behavioral model of the effects of LSD and related hallucinogens in cats (27). This model was based on the observation that cats given LSD demonstrated two dose-dependent behaviors (i.e., limb flicking as if the cats were trying to remove some foreign substance from their paws and abortive grooming as if they had been interrupted during the normal grooming act) that were not present with administration of non-psychedelic drugs. Recordings from the brainstem of cats demonstrating these behaviors confirmed the electophysiological observations of Dr. George Aghajanian that the behavioral effects of these drugs were associated with a suppression of a complex network of serotonergic neuron cell body groups (I will call this the S-Net) in the brainstem reticular formation (RF), primarily in the dorsal raphe nucleus, DRN (28). During the late 1970's Jacobs et al. had also been investigating the changes in activity of 300 or so of 60,000 serotonergic (5-HT) neurons which are clustered into 8 interlinked nodes or raphe nuclei, during the sleep-waking cycle in cats and had discovered that the onset of REM sleep was accompanied by the same suppression of activity in the DRN (29). They summarized their ideas in the following way:
"Thus, at the cellular level, there is a striking parallel between brain activity following administration of hallucinogenic drugs and [that] during REM sleep: a significant depression of the electrical activity of the brain's serotonin-containing neurons. The change in raphe unit activity seen spontaneously across the sleep-waking cycle may be the key to understanding altered states of consciousness. In response to a drug such as LSD, a key brain mechanism such as the serotonin system may function in a manner which is appropriate for a different behavioral state (e.g., the discharge rate and pattern during the drug experience may be that of [REM] sleep rather than active waking.) (p.279)".
In short, cats administered LSD appeared to be dreaming while awake, although this idea remains controversial (30), in part due to new findings of dissociations between drug effects on behavior and average DRN activity (31). In a later section I will make the case that fractal patterns of reorganized S-Net unit activity, in concert with dynamic changes in other brainstem and forebrain areas are more relevant to understanding drug effects than average DRN unit activity. Do cats dream?(Top) Work in the early 1970's by Michel Jouvet and collaborators involving small lesions in the pontine reticular formation (PRF) of cats has provided a partial answer to this question (33). The PRF, located just behind the DRN in the midbrain, is linked with the source of PGO3 waves which are responsible for phasic4 eye movements and the twitching of whiskers, ears or paws in dreaming cats. Just behind the PRF is the bulbar RF, site of origin for postural atonia or paralysis of body movements and loss of neck muscle tone called nuchal atonia (NA). NA becomes apparent when anyone tries to sleep in an airplane seat; as one goes into REM sleep NA occurs and one's head drops, usually waking him or her up. Oneiric behavior is observed in cats with small lesions in PRF after DRN activity shuts down and they enter REM sleep. As REM sleep begins, the cat, instead of having an episode of NA suddenly raises its head and moves about as if it were watching something. This type of behavior, called an orienting response, is usually associated with a heightened state of arousal and attention. For example, if you have ever watched a cat when birds are nearby, you have probably observed the birds eliciting an orienting response in the cat. During oneiric behavior, the nictitating membranes still cover the open dilated eyes as the c at pursues nonexistent prey. Many unpredictable patterns of oneiric behavior can occur; for example, predatory attack with play like pawing, followed by biting and even full rage responses can be observed (sometimes in cats who are always very friendly when awake)5. Another pattern is the occurrence of non-goal directed grooming behavior. In this case the cat will start licking its forelegs or the cage floor but would not notice a piece of paper placed on its fur. This is strikingly similar to the abortive grooming and limb flicking seen with LSD, with the exception that cats treated with LSD haven't entered slow wave sleep prior to displaying these behaviors. 1 /f Fractal Patterns in Time: The Common Ground of REM Sleep, Orienting and Psychedelic States(Top) Adrian Morrison in the same year as the Jacobs and Trulson paper, proposed a connection between REM sleep and attentional states such as orienting (36). His thesis, that cats and other mammals are in a state of more-or-less continual orienting during REM sleep, is profound in its implications for conceptualizing states of consciousness. This idea was based on his observations that similar amplitudes of PGO waves were evoked in cats during normal orienting responses to loud sounds, during normal REM sleep when behavioral orienting is absent and during elicited oneiric behavior in cats with PRF lesions (37). Other work has demonstrated that PGO waves are suppressed by 5-HT, so that cats chronically administered 5-HT synthesis inhibitors generate many more PGO waves, more orienting and display disrupted REM sleep for a period of days (38,39). In support of Morrison's idea, Yamamoto et al (40,41) have observed common 1/f fractal patterns (explained below) in recordings of interspike intervals in the RF and other regions of the cat brain during orienting to birds and during REM sleep, only not during other types of sleep or quiet wakefulness. Further, they observed that this 1/f fractal pattern is dimished by serotonergic agnoists, indicating that tonic S-Net activity during quite wakefulness and slow wave sleep (SWS) is not conducive to the 1/f state (42). In fact, nodes in the cat S-Net, such as the DRN show total inactivation during REM sleep and at the start of orienting responses, but become very active at the offset of these states (43,44). For example, during REM sleep S-Net activity resumes at the end of an epoch but at twice the rate of quiet wakefulness; this suggests that REM sleep is, at least in terms of 5-HT systems, a prolonged orienting response. Also, brain states when most S-Net nodes are inhibited or destablized, such as during REM sleep, orienting, and after LSD administration, exhibit unique 1/f fractal patterns of activity in time. Interestingly, a study from 1957 by Schneider and Sigg (45) shows that cats given ibogaine behave similar to cats displaying oneiric behaviors. They found that cats given ibogaine (2 to 10 mg/kg i.v.) show an almost immediate arousal response with rage (similar to that seen with electrical stimulation of the RF): the cats hiss as if trying to scare off an imaginary threat. This may be due to loss of global habituation to the test environment, resulting from ibogaines possible affect on the amygdaloid-brainstem pathways. EEG patterns which, prior to the injection, were charateristic of non-arousal, shifted with ibogaine to a pattern similar to that seen in REM sleep or during orienting responses. In addition, these cats displayed ataxia and a clonic extension of the hind limbs and front legs, not unlike the movement problems encountered in dogs or humans administered ibogaine. So, in cats at least, ibogaine seems to induce a REM-like state with oneiric behaviors more characteristic of PRF lesions, showing more force and intensity than low doses of LSD. I do not mean to imply by this description that ibogaine merely induces REM sleep; in fact ibogaine possesses a uniquely complex polypharmacology (46). This is often seen as a disadvantage for drugs (e.g., drugs are termed "dirty" as opposed to "clean" if they don't target a specific neurotransmitter receptor); however ibogaine's more widespread actions may in fact explain its extraordinary behavioral effects. Although this drug induced oneiric state has many of the behavioral and neurophysiological markers of REM sleep without atonia in cats, it has other unique properties which may result from a sudden massive destabilization of the normal behavioral-state- rhythmicity of the tonically firing S-Net (43), olivocerebellar systems, and other linked RF and forebrain sites. Ibogaine, effects a complex dynamic net work of interdependent dopaminergic, norandrenergic, opioid, cholinergic, and NMDA receptors and systems (46, 47). Ibogaine, like LSD, is "switching the channel" from normal attention to a dream-like state, but it is also jolting the S-Net and RF into a unique state, one that may require a return to activity patterns more characteristic of fetal ontogeny to reinstate normal functional organization. In a sense, following ibogaine treatment, the RF and associated brain regions are functionally "born again". Now that we have established a few connections between the effects of LSD and ibogaine and the behavioral states of REM sleep state and orienting in cats, we can explore how ibogaine may work through a "fetal REM-like" state in humans suffering from chemical addiction and/or PTSD. First it is necessary to review the important role of REM sleep during development and some of my recent findings concerning the fractal-in-time nature of fetal REM sleep phasic processes and their disruption by early stress. In the following sections I will describe and apply ideas from the science of complexity that may help us visualize and these unique states with 1/f patterns. The Fractal Geometry of Time in Neurobiology and Fetal REM sleep.(Top) Only a decade ago patterns of bunching or clustering in the opening and closing events of ion channels, quantal release of neural transmitters, or spontaneous patterns of firing neurons, heart beats, and breaths in the fetus or even cars on an expressway were perceived as random and uncorrelated noise-like processes (48). Many biological and natural processes are assumed to be best described as random independent processes and are still widely perceived, studied and modeled under this assumption6. However, a revolution in the scientific perception of such noisy natural processes was started with Benoit Mandelbrot's 1983 book The Fractal Geometry of Nature (49). Fractal geometry has evoked a fundamentally new view of how living and nonliving matter is organized into complex recursively nested patterns over multiple levels of space or time. Patterns termed "fractal" or "self-similar" are recurrently irregular in space or time, with themes repeated like the layers of an onion at different levels or scales. What makes this new perspective called "fractal geo metry" unique and important for understanding neurobiological processes? We are now living in an age of scientific and technological renaissance, which like the original renaissance, is a time of accelerated change and advances in many areas of human thought, particularly in the neurosciences. Dr. Rhonda Shearer has proposed in her 1998 book (51), The Flatland Hypothesis: A New Look at Revolutions in Art and Science, that the appearance of new geometries, such as the development of geometric perspective in art with the Renaissance, heralds the appearance of changes in thought and social values, foreshadowing innovations in science, art and medicine. Flatland, Edwin A. Abbott's 1884 book, referred to in the title of Shearer's work, depicts a two-dimensional world peopled by lines, squares and multi-sided polygons in a rigid hierarchal society with no concept of higher dimensions. When a three-dimensional sphere being appears as a circle in Flatland, his very existence plants the perceptual seeds of a scientific and cultural revolution. Shearer credits Abbott with the formal insight later attributed to Thomas Kuhn, author of the Structures of Scientific Revolutions, that changes in scientific thinking are linked to the individual's perception of conceptual change. If a new geometric perspective inspires innovative approaches to fundamental scientific questions, then the importance of exploring and incorporating the useful insights derived from the fractal perspective should not be underestimated. Echoes of similar perceptual revolutions are familiar to the readers of MAPS in the work of Stanislav Grof, Albert Hofmann, John Lilly, Timothy Leary, Claudia Naranjo, Alexander & Ann Shulgin and many others7. It is the contention of the author that without this well-rounded viewpoint on the spontaneous aspects of brain and behavior activity at all levels of organisms, the biological, medical and neurosciences may become trapped in a kind of conceptual and experimental "Flatland ". What is a fractal and why should one be mindful of it? Benoit Mandelbrot coined the word fractal from the Latin adjective fractus,infinitive frangere, meaning "to break" and create irregular fragments. The concept of fractal is, can be a way of creating a seamlessly unifying view of the physical and biological world, perhaps even our very consciousness, as long as the concept is applied flexibly (53) in a "free play of ideas (50)" . The World-Wide-Web (WWW) is possibly the best place to see and learn about fractal concepts in general, and their applications in biology and psychology or just to educate the eye to the endless possibilities of fractal forms. The term fractal applies to objects in space or fluctuations in time that possess a form of self-similarity: fragments of the object or sequence can be made to match the whole object or sequence by shifting and stretching. Fragments of fractal objects can be exact or statistical copies of the whole. Mathematical fractal objects visually convey the concept of self-similarity. However, only fragments of mathematical fractal objects can be exact copies, and exactly represent the concept of self-similarity, whereas the fragments of natural fractals are only statistically related to the whole. Another way to think of fractals is in terms of clusters of points or events in space or time. Self-similar clusters have smaller clusters within larger clusters of clusters. Clouds, broccoli, or the surface of the brain can all be visualized as clusters of clusters in space. These clustering patterns, described as bursts within bursts, are a universal characteristic of spontaneous behavior in living systems of cells, neurons and the early motitily of embryos of both vertebrates and invertebrates (54). Self-similar burst-within-burst patterns are ubiquitous, observed in ion channel currents fluctuations (55), neurotransmitter release (56), neuronal firing patterns (57), the searching patterns of animals (58,59), human judgment and decision making (50, 61) and traffic patterns both on expressways and over computer networks such as the WWW (62). Examples of the burst or clustering patterns are, in fact, familiar to anyone who has driven in or observed highway traffic from a passing airliner. Rush hour or holiday traffic slows to a stand still due to the tendency of nearby automobiles to spontaneously cluster together, forming larger and smaller jams of all sizes. The pervasive nature of these self-similar clustering patterns is again apparent when trying to gain access to the Internet during peak times. Although the self-organized fractal burst patterns common to both traffic situations appear to be only epiphenomena, they place fundamental constraints on traffic flow. In sharp contrast, biological systems appear to thrive and grow via self-organized fractal burst patterns. In the following, I will attempt to sketch the self-organized critical state, and its possible presence in traffic patterns, developmental and cognitive processes. This concept, although still in its infancy, may provide a foundation for understanding the association of 1/f fractal time patterns (63, 64) with REM sleep, orienting and the therapeutic effects of oreiric substances such as ibogaine. Self-Organized Critical States in Ion Channels and Traffic Jams on the Road or the Web: A Bridge from Clusters of Molecules to Clusters of Minds.(Top) At first glance, perhaps, it is disorienting to be reading about fractal patterns of highway and internet traffic in an article on REM sleep and ibogaine. Nevertheless, complex systems like traffic or large-scale cortical networks share universal characteristics that in one way or another lead to the reoccurrence of similar patterns in very different systems. The great benefit of the sciences of complexity is a perspective that affords open mindedness to concepts linking diverse fields and applicable to any level of biological or physical description. One such concept is that of the self-organized critical (SOC) state, which describes how complex spatially distributed entities, such as traffic networks, interact across many time and space scales. This concept was originated by Per Bak, a physicist, to explain the widespread presence of 1/f fractal patterns in time (63, 64) in nature. The fluctuations of many phenomena- flow of the Nile, light from quasars, ion channel currents, neuronal firing patterns, earthquake distributions, electrical current fluctuations in man-made devices, inter-car-intervals in expressway traffic, and in variations in sound intensity in all melodic music (65), have been found to exibit 1/f patterns. The sound of 1/f noise in a transistor is described by Machlup (66): "...the 1/f noise sounds like pshsh, ktshsh, pdk, kshsh... You can hear the individual events. Big events are less frequent than little events. "Twice as big occurs half as often." In general, 1/f noise is fractal with respect to time, because the same processes "...pshsh, ktshsh, pdk, kshsh..." occurring on one timescale, say recorded over microseconds, is self-similar to a "...pshsh, ktshsh, pdk, kshsh..." occurring on another timescale recorded over minutes. The Sandpile model, developed by Bak and his colleagues, provides an intuitively simple description of the mysterious ubiquity of 1/f fluctuations. As grains of sand are added to a pile of sand, a number of processes begin to occur. The added sand will accumulate giving the pile a slope. Now and then, as the sides get too steep somewhere on the pile a single grain causes a sand-slide or avalanche. The sand pile stops growing in height as it reaches a characteristic or "critical" slope, and at this point the sand pile is in what is termed the SOC state. Avalanches of all sizes can occur with the addition of a single grain of sand at the critical state; however, on average, large slides occur less frequently than smaller slides. In fact, over time the pattern of large and small slides is 1/f. Again, "Twice as big occurs half as often." Bak interprets this as suggesting that 1/f noise "...is the superposition of signals of all sizes and durations--signals produced when a dynamic system in the critical state produces chain reactions of all sizes and durations (63; p.48)." The concept of a SOC state allows you a new way of understanding and visualizing the organization and interaction of complex phenomena over many scales of time or space. For example, work using simplified models of traffic flow indicates that, in situations where the highway is filled with cars on a highway, usually on holidays, fractal clusters of traffic jams of all sizes are more likely to occur. Traffic tends to self-organize into a critical state, where small fluctuations can lead to traffic jams of all sizes or magnitudes and the 1/f signature. For example, when one driver breaks too soon or too late, an avalanche of stops and starts is propagated for great distances over the highway, resulting in long-tailed distributions of inter-car-intervals and long-range correlations between the behavior of drivers miles apart. Contrary to intuition, possible steps to reduce jams, for example, mandating automatic car-following systems, have been found in mathematical simulations to paradoxically push traffic closer to the critical point where jams of all sizes are more likely to occur. What new insights can SOC bring to REM sleep, orienting and psychedelic states? REM sleep, Orienting and the Psychedelic Experience as Self-Organized Critical States: Coalescence of PGO Activity into Oneiric States.(Top) The concept of SOC has only been used, thus far, to describe behavior in homogenous populations of sand grains or cars, where each interacting element is nearly identical. The brain, in terms of neurons and connections, couldn't be more heterogenous. Heuristically, SOC may help us to visualize a common critical state that exists throughout the brain and brainstem, during states of REM sleep, orienting or those induced by LSD and ibogaine, resulting in 1/f patterns of interspike intervals as observed by Yamamoto et al. I propose that PGO spikes8 and other phasic activity during these states, are analogous to the sand slides or traffic jams of all sizes, representing critical fluctuations in neural activity and connectivity. The SOC state during the orienting response, may facilitate rapid functional brain reorganization in response to the qualities of the eliciting stimulus. The critical connectivity that exists during these states may primarily involve orienting synergies (among ocular, neck and facial motorneurons). PGO waves may link this critical brainstem centered connectivity with limbic and cortical structures such as the amygdala and temporal lobes. PGO spike density increases as tonic REM sleep begins, suggesting, as Morrison observed, that REM sleep is a dense, coalescence cluster of PGO activity. From the fractal point of view, REM sleep is a kind of fractal of PGO bursts, and in support of this image, bursts of fine finger twitches during a single REM sleep period appear statistically self-similar to sleep architecture over the entire night (see 67; Fig. 1-7 for example). With eyes closed, during the oneiric state, PGO-like9 amoug amygdaloid and brainstem sites, could generate and direct waking dream sequences. After drug effects subside, with the return of tonic, stereotyped S-Net activity, the natural tendency for PGO spikes to coalescence is forced back into the discrete patterns we know as the nightly periods of REM sleep, constraining the daytime expression of this critical state of connectivity to orienting attentional states (38). 5-HT neurons during quiet wakefulness fire in an almost stereotyped, clock-like-pattern at 1-5 spikes per second (43,44). When a cat begins to groom or chew, the S-Net fires at 2-5 times this rate. Jacobs and Fornal have proposed, that in fact, S-Net activity facilitates stereotyped motor output patterns and concurrently inhibits sensory input (44). If the cat is distracted during grooming, the S-Net pauses to allow sensory processing, and possible motor system functional reorganization, otherwise it returns to grooming. S-Net activity, in concert with dopamine release in the basal ganglia, appears to facilitate functional connectivity among clusters of cortical-striatal-thalamic loops during motor output (44). I would go further, and suggest that complex habitual sequences of motor output (e.g., drug seeking and drug consuming behavior in addicts) represent hypercomplex sequences of cortical-striatal-thalamic activation, triggered by sensory dependent amygdaloid-brainstem modulation of the monoaminergic systems during critical states. The power of ibogaine to break habitual patterns of addiction may reside in an induced SOC state that disrupts and functionally reorganizes this amygdaloid-brainstem system (32, 68), in effect resetting the brain/mind. Fractal Bursting and Clustering During Ontogeny: Lévy Stable Distributions and Vertical and Horizontal Integration During Brain/Mind Self-Organization( Top) My underlying thesis is that ibogaine works on many brain systems to drive firing dynamics into a SOC state with avalanches of phasic events similar to that existing during early development. To fully explore this thesis I will show how different development processes and disorders can be reconceptualized in terms of phenomena involving fractal clustering based ideas such as SOC, Lévy stable distributions and vertical and horizontal integration. During embryonic development, cell division creates a ball of cells, which will if all goes well, self-organize into a coordinated interconnected system of tissues. Concordant with cellular and molecular differentiation into tissues and organs is the development of functional connectivity among these complex systems of cells. This formation of functional connections and interactions from molecules and cells to tissues and organs, I will term "vertical" integration (69, 70). I will call the development of functional connections within a level of organization, say within a group of polyinnervated muscle fibers (71), "horizontal" integration (see below). Biological systems are in a constant state of criticality and self-organization. In contrast to highways and traffic jams, analogous critical states in developing brains may lead to the enhancement of synaptic connections, sparing of axons, and synchronizing twitches that allow distant regions of the organism to link and coordinate gene expression and neural-motor development. Traffic jams on the internet are almost as complex because of the highly interconnected nature of computer networks, and the vastly different timescales, from microseconds to seconds and hours, are closer to those present in developing organisms and the brain. Information travels over the internet in the form of packets with a wide range of sizes. As a result, the occurrence of bursts (packet traffic jams) is more pronounced. Long patterns of bursting have statistical self-similarity and 1/f power spectra; in some cases, they appear very similar to the bursting patterns of ion channels, neurons and phasic REM processes such as PGO waves (compare Fig 1 and Fig 2). WWW bursting patterns originate in the complex interactions among computer processes, network dynamics and user "think times"(62). For example, the cognitive psychologist D. Gilden (60,61) has found that fractal time variation is a basic element of human judgment and decision making, implying that the user and his or her fractal processes, through vertical and horizontal convergence over the network may supply some of the fractal bursting present in the WWW. Recent fractal models of internet traffic have been successful in illustrating many of its characteristics, including self-similarity, long-range correlations, and clustering that results in long-tails (72); such models can give us a way to visualize complex developmental processes. In these models, the superposition or cumulative counting of many packet trains with different short- and long-time characteristics generates self-similar traffic traces, with Lévy stable distributions. What are Lévy stable distributions? Self-similar clusters in time result in unusual statistical properties. For example, the mean and/or the variance may grow with the sample size, becoming for all practical purposes very large or infinite. Mandelbrot, who first observed these strange statistical properties in the price changes of stocks, cotton, and other commodities, commented: "To any one with the usual training in statistics, an infinite variance seems at best scary and at worst bizarre (p.338)." These curious qualities are the result of large intervals or so-called "outliers" among the clusters, which give plots of the distribution of inter-event-times long or heavy tails. While not Normal or Gaussian, these distributions are related through the stable Lévy model, a mathematical space of possible distributions (73, 74). For example, for Gaussian distributions, as the sample size is increased, the mean and variance both converge; in Lévy space, Gaussian distributions are mapped to a point in this space, a = 2 (derived from fitting an exponent to the tail of the distribution). Non-Gaussian distributions with a finite mean, but infinite variance, have exponents in the range 1< a < 2. Lévy exponents are a simple way to measure distributions generated from self-similar clusters or bursts in time. A unique property of distributions that fit the Lévy model is a mathematical form of vertical convergence called "convolutional stability." Stable distributions like the Gaussian or even those with infinite variance vertically integrate into larger stable distributions and are therefore self-similar over different sample sizes or time scales. Psychedelic Drug Induced Fractal Clustering in Serotonergic Network Output Patterns (Top) Fractal clustering provides new ways of thinking about the behavior and interrelationships of networked brain systems. For example, the S-Net enmeshed in the RF (43) and interlinked with other monoamine, cholinergic and peptide systems could, like the WWW, be visualized as a backbone of primary nodes, with links to secondary networks and nodes. The differential effects of psychoactive drugs could be mapped to changes in the SOC state of the S-Net, knocking out the activity of some nodes and resulting in atypical fluctuations in 5-HT release in different brain regions (68). For example, LSD, 5-methoxy-DMT and Psilocin have primary effects on the DRN, the nucleus centralis superior (NCS) but little effect on nucleus raphe pallidus (RPA) activity. On the other hand, phenylethyamine hallucinogens have few effects on NCS or RPA activity (75). These fractal fluctuations in S-Net activity may synergise with drug effects in other neurotransmitter systems to bring new qualities to self-organized critical oneiric states. LSD, unlike 5-methoxy-DMT and Psilocin has effects on cortical-limbic dopaminergic cells in the ventral tegmental area (VTA) of the midbrain, resulting in enhanced dopamine relese in the amygdala and prefrontal areas. The duration of these drug effects has broad range of time scales, and may fluctuate wildly as the S-Net tries to reinstate stereotypical stability. The resulting alterations in synaptic flux of monoamines may influence the degrees of segregation or clustering of functional subcircuits of various bilateral brain regions such as basal ganglia, amygdala and cortical areas which, in turn feed back on the subnets of monoamine cell body groups. Ibogaine, due to its complex polypharmacology and active metabolite which is a selective 5-HT reuptake inhibitor (SSR), may prolong S-Net reorganization during therapy. Thus, systems with fractal bursting patterns over many time scales, such as the WWW, may provide general models for drug action or neurodevelopmental processes. The Fractal Structure of REM Sleep in Fetal Sheep(Top) The REM-like sleep state is pervasive during fetal life, playing an essential, but up to now, unexplained role in the developmental organization of brain and behavior (76). In 1996, Dr. Mandell and myself proposed that the correlated fractal bursting nature of REM, or Active sleep, as it is sometimes called in the fetus and newborn, provides an invariant stable Lévy temporal framework in which cortical and subcortical networks can organize and consolidate changes (77). The central focus of my doctoral research, underway at the time I met Dr. Mash, was to test this proposal (78,79). I measured the durations of NA over extended periods in fetal sheep and neonatal rats, species which are in a REM sleep-like state > 50% of the time. I found that the recorded NA episodes demonstrated the expected developmental changes reported for other REM sleep markers, as well as non-random fractal clustering patterns in time during the last trimester in fetal sheep (79), and during the first 12 days of life in neonatal rats. Also, analysis of the Lévy stable characteristics of NA sequences demonstrated species invariant activity: NA a = 1.8 for both fetal sheep and neonatal rats for all ages. These findings are striking in that they illustrate that phasic REM associated events, at least during development, are not fundamentally independent random processes10, as is implicit in Allan Hobson's activation-synthesis model of REM sleep, but rather are fractal in time. I assert that fractal time Lévy processes can be used to characterize the phasic events associated with fetal and adult REM sleep, such as eye movements, and may have great significance in understanding the relationship between REM sleep, neural plasticity and ibogaine therapy. The Puzzle of REM Sleep in Sickness and in Heath: A Common Fractal Thread?(Top) Why do fetuses spend most of their time and energy in a state with strong similarities to adult REM sleep? They are apparently not in need of many of the functions ascribed to adult REM sleep, although young animals deprived of REM sleep exhibit behavioral defects through life (82). What is the functionof adult REM sleep? By the time we reach the age of 70, on average, we have spent 8.5% or 6 years of our life in REM sleep. Why is REM sleep such an important component of our lives? In fact, REM sleep is almost as essential for life as water and food. For example, the work of Rechtschaffen et al. (83) demonstrates that chronic REM-sleep deprivation will kill adult rats in three to four weeks. REM deprivation is also a basic technique used during torture, brain-washing and interrogations, leaving survivors with life-long PTSD associated sleep disturbances and low dream recall (84). Could the fractal properties REM sleep I have described in fetal animals provide a common thread between fetal and adult REM and insights into disorders of REM sleep? Disturbances of phasic REM processes are also a common thread in many disorders of sleep in infants, children and adults (4, 85, 86, 87). As mentioned earlier PTSD is linked to a fundamental disturbance of phasic REM sleep mechanisms resulting in recurrent stereotypical anxiety dreams as well as disturbed limbic system and brain stem-mediated functions such as abnormal startle responses (1-5). Chronic use or abuse of many drugs results in alterations of phasic REM sleep processes (86). Delirium tremens or "the DT's" that follow withdrawal from chronic alcohol use appears to represent an intense period of rebound REM sleep accompanied by waking hallucinations (88). Analogous to ibogaine therapy (see below), recovery from an episode of DT's is followed by a prolonged bout of deep, refreshing sleep called "terminal sleep" from which the patient awakens essentially recovered from withdrawal (89). Temporal lobe dysfunction involving limbic structures such as the amygdala and hippocampus are frequently associated with sleep disturbances and REM sleep-related events such as sleep walking and parasomnias (35, 90). Disorganization of sleep architecture over many timescales (from microstructure to circadian structure) is commonly associated with many psychiatric illnesses, including anxiety disorders (91). Hemispheric asymmetries, resulting from lateralized temporal lobe dysfunction and alterations of commissural development (11), the aftermath of childhood stress or trauma, could represent another key factor in sleep disorders. General models proposed for REM sleep function in adults do not usually provide a common theoretical foundation for understanding and incorporating these disorders. Moreover, most theories of adult REMS function ignore its central role during fetal life or, on the other hand, claim that adult and fetal REMS are too different to be considered relevant to adult behavior (93-94). In the following I will describe how alterations in the vertical and horizontal consolidation of self-similar bursting patterns of phasic sleep events can provide a conceptual bridge between the disorders of REM sleep in adults and in children. This conceptual foundation underlies my hypothesis of ibogaine action in bihemispheric reintegration. Dueling Amygdalae in Sleep Pathology : Insights into Autism and Interhemispheric Reintegration Via REM Sleep(Top) Recent work on the neurobiology of autism has implicated bilateral medial temporal lobe structures such as the amygdaloid complex as key brain sites of the socioemotional abnormalities seen with this severe developmental disorder (95, 96) although many other brain regions have also been implica ted. The amygdaloid complex composed of two almond shaped structures deep in the medial temporal lobe (amygdala is latin for "almond") appears to play a permissive roles in REM sleep onset, sleep architecture and ultimately dream content. For example, amygdaloid stimulation in unrestrained cats evokes significantly increased PGO number, spike and burst density (97). Regional cerebral bloodflow in the human amygdala is positively correlated with REM sleep (98). The central nucleus of the amygdala is reciprocally innervated by brainstem regions, such as the parabrachial region which is involved in alerting and in the generation of REM and PGO waves (68). Also cholinergic activation of the central nucleus produces long-term facilitation of REM (32). In addition, the amygdala receives most of its serotonergic innervation from DRN which has a strong inhibitory influence upon amygdaloid neurons (99). LSD may disinhibit amygdaloid neurons and has also been reported, at low doses, to increase the duration of REM sleep periods (14). Symmetric activity in bilateral amygdaloid-parabrachial pathways may be required for the occurrence of typical global sleep architecture during a nightly sleep period. As is seem in amygdaloid kindling in cats (100), asymmetric hemispheric activation of amygdaloid-parabrachial pathways results in abnormal sleep architecture and pronounced changes in the patterns of phasic REM events. How might temporal lobe dysfunction associated with amygdaloid-parabrachial pathways in autism manifest in patterns of phasic REM sleep? Tanguay et al. (101), have investigated the phasic clustering nature of REM in autistic and normal children, through their observation of ontogenetic changes in the bursting structure of eye movements (EM) during REM sleep. They found that eye movements in normal children on the whole did not become organized into bursts until 40 weeks gestational age; thereafter changes in the clustering of the bursts of EM were correlated with developmental age. Also, from 2 to 24 weeks postnatal, as total REM decreases, the number of EM's remain constant resulting in an increase in the mean number of EMs/sec of REM. This recurrent theme in many developmental processes, horizontal integration or the coalescence of clustering with age, as described for NA, was observed in normal children between 3 months and 5 years of age. At this age, a major organizational change occurred in the patterns of EMs, marked by the increasing tendency of bursts of EMs to cluster, with more and shorter EMs packed into bursts within bursts. However, autistic children were found to have substantially less clustering of EMs. In fact, no significant differences between burst structure in 2-5 year old autistics and younger (<18 month) normal children could be found. If the horizontal integration of fractal patterns at different levels of the CNS is a valid concept, then the autistic children seem to display a failure to complete integration at this stage of development. It's as if they are stuck at one dynamic stage of development, unable to progress. Perhaps functional dynamics of abnormal asymmetric cortical-amygdaloid-parabrachal pathways are involved (95) and hinder horizontal integration promoting excess phasic activity imature global sleep architecture. Increased phasic activity, analogous to fetal activity, could be an attempt by the brain via enhanced bursting to establish long-range correlations and promote horizontal integration. Successful behavioral therapy for the treatment of autism by sustaining long-range fractal correlations between events in the emotional-behavior experience of the autistic child may enhance horizontal integration within these pathways. Lévy measures of the clustering of phasic REM processes could provide a useful assessment of the progress of behavioral therapy, as well as other therapeutic approaches to mental illness. During development horizontal integration should be viewed as concurrent with vertical consolation of fractal clustering. In the following section reductions in phasic events will be conceptualized as a disruption of vertical consolation, in light of the fact that simultaneous changes in horizontal integration are also taking place. Vertical Fractal Clusting: Insights into Developmental Stress, Trauma and PTSD. (Top) I have demonstrated that fractal clustering of NA in different species appears similar (78,79). However, one experimental confound of measuring NA in neonatal rats is maternal deprivation. Neonatal rats are entirely dependent on maternal care, as are human newborns. Periods of isolation are therefore severe stressors for neonatal rats. The neonatal rats I tested were subjected to two hours of maternal deprivation over the course of the procedure, and I noticed that their patterns of twitching seemed changed at the end of recording. When I comparing NA patterns (across all ages) during the first 5 minutes of testing with the last 5 minutes, maternal deprivation caused an a decrease in the Lévy exponent from a 1.8 to 1.6 indicating that NA became more clustered in time because of longer periods of NA. This represents a major finding of my work: maternal deprivation, a model of early abuse, results in alterations of fractal measures of clustering such as the Lévy exponents, shifting distributions from their normal species invariant values. Later work confirmed that these shifts persisted into adult spontaneous activity (6). Unlike autism which failed to show normal coalescence of EM clustering with age, early deprivation results in disruptions of vertical integration of clustering patterns, leading to fewer but larger NA events. Also, this early abuse induced change persists into adulthood, similar to symptoms of PTSD associated with child abuse (102, 103). Lasting changes in the amount or pattern of phasic activity associated with REM sleep appears to be one common thread linking PTSD and other sleep disorders in children and adults. Functionally asymmetric cortical-amygdaloid-parabrachal pathways could also be a critical common factor in PTSD and other psychiatric illnesses. Autism and materinal deprivation both appear to indicate that transformations in the quantities or characteristics of phasic REM processes may be a compensatory mechanism by which the brain attempts to reestablish horizontal and vertical consolidation through correlations inherent in the clustering process (78). In the following, a theoretical explanation of the sequential stages of ibogaine experience during treatment will be attempted in the context of hemispheric asymmetry, phasic REM processes and the psychobiology of the amygdaloid complex. Emotional Memory, the Amygdala and Tripping in Fractal Time: Going Back to the Womb with Ibogaine(Top) During ibogaine therapy11 patients have reported a dose-dependent experience of dream-like states, except that they are awake and can respond to questions. Soon after administration, the patient:
1) first experiences a loud humming or oscillatory sound, changes in visual perception and signs of ataxia when trying to walk;
2) Within 1 to 2 hours this auditiory experience ends and images may appear, especially after eyes are closed. The patient then notices a rapid visual presentation of various images, sometimes specifically reviewing traumatic events or circumstances from their childhood and/or life of addiction for a long period (3 to 8 hours). Distortions of time perception by the patient are also reported, in which the dream experience is perceived to take less much less time.
3) Following the sudden end of dream stage (3 to 9 hours post adminstration), a period of intensive reevaluation of previous life experiences can take place. The stimulant or opiate-addicted patient may then sleep for long periods, and awaken without characteristic withdrawal symptoms (analogous to "terminal sleep" following DT).
4) Long term effects of the ibogaine treatment include a reduction in the need for sleep to 3-4 hours per night for up to a month or more and the elimination or amelioration of the craving and desire to do drugs.
This is a general description of the ibogaine experience and many variations in the length, occurrence or quality of stages are often observed.
1) The Pervasive Oscillatory Sound
During this stage, the pharmacological effects of ibogaine and its primary metabolite may start to destablize the habitual amygdaloid-brainstem modulation of global bihemispheric monoaminergic systems. The disturbing effects of lights and sounds could result from loss of normal global habituation due to RF destabilization, resulting in the fear and rage responses observed in cats. Trauma or drug abuse history is strongly associated with asymmetric hemispheric function (7-11, 104, 105) and recent anatomical MRI and fMRI data show that temporal lobe structures such as the hippocampus and amygdala are particularly sensitive to the effects of child abuse and trauma (9,21). The oscillatory sound could indicate rapid shifting or cycling of attentional resources between the left and right hemispheres, possibility in association with pharmacological downshifting of the normally constant 10 Hz rhythmicity of the olivocerebellar system (106). This sign may be stronger in subjects with more pronounced asymmetric hemispheric function and awaits further investigation. As this oscillatory auditory effect downshifts, possible flooding of the left hemisphere by material from the uninhibited right may takeover primary conscious focus, as outlined by Mandell and Geyer (14). This sets the stage, along with phasic fluctuations of the S-Net and uninhibited PGO, for the sudden onset of the SOC state and the waking dream period.
2) Waking Dreams: A Healing Journal Through the Fractal Hyperspace of Emotionally Indexed Childhood Memories
I propose that the basolateral amygdala (BLA) is a critical neural substrate of the waking dream stage as fractal neural bursting in this subcortical cortex-like structure may represent access points in a fractal hyperspace of emotionally indexed memories23. The effects of early trauma on the development of the amygdala and other temporal lobe structures may interfere with its normal bilateral function during REM-sleep mediated consolidation of emotionally significant events. The recall of traumatic childhood experiences in adults, due to the immaturity of limbic structures at the time of trauma, my require electrical stimulation or intensive PGO-like activity present during the ibogaine oneiric state. Habitual disruption of normal sleep processes by stress associated with combat, bereavement, divorce, child abuse, neglect or chronic drug abuse interferes with the natural restorative function of phasic REM process, resulting in patho-neurophysiological sequelae of events further exacerbating physiological and psychological addictions and rigidifying emotional traumas into PTSD and chronic hemispheric imbalance. Ibogaine mediated exploration of the subspaces of emotional memories associated with these traumas may help to free these rigidities, restoring after cognitive reevaluation and horizontal and vertical consolidation of amygdaloid-brainstem systems, some degree of normal hemispheric balance. The amygdala, is also known, from many studies in animals and humans to act as the meeting place between emotions and the mind. Vietnam Veterans with PTSD, for example, have increased rCBF in the right amygdala when generating mental images of combat-related pictures (104). We each have bilaterally interacting right and left amygdala which give us our internal emotional experiences by processing and attaching affective response to the rich flow of information from all the five senses and modulating our perception and the autonomic centers of the brain. Extensive research involving patients with temporal lobe epilepsy originating in the BLA has demonstrated that emotional experiences, in some cases highly charged, can result from electrical stimulation of this area. Although these experiences cover the full range of human emotions, fear and anxiety are the most common and are evoked frequently from the right amygdala. The following, from Gloor et al. (107), is a description of a childhood trauma memory evoked during electrical amygdaloid stimulation in an adult male prior to surgery:
"When the right amygdala was stimulated with a 1 mA current, {the patient} experienced something that he found difficult to describe but finally likened to a feeling of falling into water. {after another stimulation} The patient immediately opened his mouth with an astonished look on his face, sat up, and said that now he knew what it was: it was the feeling of being at a picnic in Brewer Park in Ottawa. "A kid was coming up to me to push me into the water. It was a certain time, a special day during the summer holidays and the boy was going to push me into the water. I was pushed down by somebody stronger than me. I have experienced that same feeling when I had petit mals before. {...} When questioned whether he actually saw himself being threatened by the "big fellow" he said no, but it was a feeling as if he were there and was being chased."
Thus it appears from the work of Gloor (107, 108) and many others that the amygdala, particularly the right BLA, is where the "right mind" and brain meet to generate and bring to awareness the associated memories and emotions of a traumatic experience. Ibogaine may evoke the appropriate fluctuating milieu of neurotransmitters and neuromodulators to trigger a SOC state in the BLA, amygdaloid-brainstem pathways, and extrastiate areas activated during dreaming (109). The unique morphology of the BLA pyramidal cells and lack of tangential or radial cortical organization may reflect functional connectivity specialized for non-sequential interactions over multiple timescales (or broad-band synchronization) with other temporal lobe cortical and subcortical regions. Distortions of time perception noticed by patients may reflect the "rescaling in time" afforded by the fractal bursting of BLA pyramidal cells during this critical state (77). Taken together, these observations, speculations and experiences point to the role of common SOC states in the amygdalae, extrastriate cortex and brainstem, as the emotional and visual and substrates for ibogaine "experiential" dream-like phenomena.
3) Reevaluation and The Long "Terminal Sleep"
After the abrupt end of the SOC dream-like state and rapid image experience subjects are able to reflect on and integrate the experience, free of craving or withdrawal symptoms. The subject has experienced "the big picture" and a unique perspective on his or her life. If struggles between the twin minds underlay drug addiction, then the "experiential" recall of trauma experiences may help bring understanding and insight to these struggles. Many addicts report a feeling of "getting in touch with their soul" or a feeling of oneness with the universe and that "...all the people in the universe and all things in the universe are only one." These experiences and feeling, in part, may result from a new sharing and harmony between long dissociated twins. A long period of sleep may then ensue, and patients after waking have reported having had "the best sleep of their lives." As described above the sequence of stages in ibogaine therapy has some interesting similarities with Delirium tremens and terminal sleep that follow withdrawal from chronic alcoholism and other kinds of drug addictions. In this regard, the ibogaine state may represent a kind of facilitated "REM-rebound" process, making up for sleep loss since tramua or abuse first affected sleep architecture.
4) Recovery and Insomnia
In the month following ibogaine therapy insomnia may be due to the presence of a long lasting metabolite (Mash, personal commucation) and/or a reduction in the physiological need for sleep because of the intense emulation of dreaming (or REM rebound) which occurs during the treatment. This intensifies adjustment problems for addicts, due to the lost of old patterns of behavior and social support during this phase. Among The Fang, where eboga is used ritually, a strong social network already exists. After initiates recover for their "journey to the land of the dead," the are reborn socially, and have new social status. One of insights that the fractal perspective can bring to psycho therapy is the necessity of the "long-view". Although the brain generates long-range correlations, abuse, trauma and the stress of modern life can quickly destroy these correlations. While the ibogaine experience my restore long-range correlations through SOC and horizontal and vertical processes, it is also necessary to complement these sources with support groups, long-term therapy or follow-up as well as community involvement and reintegration. A supportive social network, as with The Fang, should be a fundamental part of any large-scale ibogaine treatment program. Summary and Future Directions(Top) I have presented a comprehensive hypothesis supporting the use of ibogaine (and other oneiric substances) in the treatment of chemical dependency and PTSD due to its unique neuropharmacological and psychobiological properties. These two disorders are usually interrelated in that the majority of drug addicts have a history of traumatic abuse that may result in functionally abnormal hemispheric interactions precipitating emotional instability and addictive behaviors. In the hypothesis I proposed that ibogaine works through multiple neurotransmitter systems to create within amygdaloid-brainstem systems a self-organized critical oneiric state or state of plasticity, similar to states of plasticity existing during fetal development. This critical brain state may facilitate the consolidation of traumatic memories, reversal of abnormal hemispheric functional and the dissolution of habitual motor patterns associated with addiction. It is the hope of the author that this hypothesis may provide a spring-board for experimental investigations of many of the related ideas presented, providing an integrated theoretical view of the action of ibogaine and other oneiric drugs, with the final goal being the introduction of ibogaine or other oneiric compounds into widespread clinical use.
The following are a few proposals for further research with this goal in mind:
Measurement of Phasic Events in Addicts Pre- and Post- Ibogaine:
With relatively little expense, non-invasive measurement of EM's or GSR before, during and after ibogaine therapy could be carried out in addicts undergoing treatment. Changes in the fractal clustering of phasic events such as EM's or GSR may provide a useful objective assessment of the progress and long-term effects of therapy. Also, LVFS goggles and ear temperature measurements could provide correlates of hemispheric asymmetry changes (18,19,21).
Measurement of changes in hemispheric functional with ibogaine:
A much larger study to assess changes in hemispheric asymmetry using quantitative EEG, PET imaging or functional MRI measures of brain activity pre- and post- ibogaine, could test the dual hypothesis that hemispheric asymmetry is involved in addictive behavior and that ibogaine may ameliorate these asymmetries. Pre- and post-ibogane sleep studies could also explore the relationship between hemispheric asymmetry, addiction, phasic events and general sleep architecture. Due to the more invasive nature of this testing, and the lack of testing facilities in countries where ibogaine is legal, these studies could not be performed at this time during actual ibogaine treatment. Acknowledgements(Top) First and foremost, I thank my wife Mary R. Kolodny for her expert editorship, companionship, patience and love during the long four years this paper took to write. Support has been provided by the Center for Complex Systems and Psychology Department at Florida Atlantic University and now by a supplement to (MHT's) NIMH ROI-53636-01A1 supporting the recruitment of individuals with disabilities into biomedical research careers. This paper would not have been possible without the insights and inspirations derived from many insightful conversations over the years with Drs. Arnold Mandell, Marty H Teicher, Fred Schiffer, Tim Iverson, Leslie Terry and many others. Special thanks to Drs. Debora Mash and Julie Staley for their critical contribution and the clarity of their vision. References(Top) 1. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder Am J Psychiatry (1989 Jun) 146(6):697-707.
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109. Braun AR et al., Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep. Science, 279:91-95 (1998). Footnotes:(Top) 1.The term "REM sleep" describes one of the universal signs of dream or paradoxical sleep in adults, rapid lateral movements of the closed eyes. This term is also used as a kind of "shorthand" for a constellation of other associated "phasic REM sleep processes" or dream sleep signs (e.g., loss of neck or nuchal antigravity muscle tone, desynchronized EEG, limb twitches, etc.). Whether fetal Active sleep i s accepted as homologous with adult REM sleep depends on the point of view of the researcher. Here I will side with the argument of Blumberg and Lucas (1996) that "...sleep is not the product of any single, essential controller [or sign] but an emer gent property of the dynamic interactions among individual [phasic] components (p.4)."
2. Sadly modern neuroscience has become progressively "left-brained" in its approach to integrative neuroscience over the last decade, with an over emphasis on molecular approa ches, at the expense of neural-behavioral synthesis (this trend is evident in the progressive deletion of behavioral categories in the Society for Neuroscience Annual Meeting Program from the 1980's to the 1990's). ; 3. PGO waves (P for pons, G for [lateral]geniculate, and O for occipital cortex) are generated by cholinergic burst cells in the peribrachial region that convey phasic act ivation and eye movement information to the lateral geniculate, amygdaloid region and visual cortical areas. The amygdaloid region [see below] is reciprocally connected with the peribrachial region and has recently been placed on equal footing with the b rainstem in the genesis of phasic RE M phenomena (32).
4. Guiseppi Morruzzi (34) in the 1960's first noted that REM sleep could be descriptively divided into tonic events, or events that last throughout an entire REM episode, and phasic events that could be characterized as "outbursts" of activity on a relatively stable background of activity.
5.This same behavio r occurs in people with brainstem lesions (35).
6. Bohm and Peat (50) commented on how a breakdown in communication in scientific work can result from different and incompatible ways in which the informal language of science is used. Take, for example, the word random: random numbers from a computer generator appear to lack any degree of order, when in fact the numbers are produced in a very ordered and deterministic fashion. Randomness is relative and context dependent. The definition of randomness as lacking all order "has no real meaning...[because]....random events do happen to take place in a definable and describable sequence and can be distinguished from other random events....in this elementary sense they obviously have an order (50; p. 128)." Perhaps neuroscience should adopt the working hypothesis that complex spatial and temporal order in neurobiological systems frequently appears random, but may not in fact be as random as the decay of a radio isotope until measured and proven.
7. See Combs (52) for an elegant summary of many of the new and emerging concepts of consciousness inspired by nonlinear dynamics, transpersonal psychology and LSD.
8. These trigger PGO waves, the large phasic slow electrical potentials that can be measured over widespread areas of the brain.
9. K-complexes maybe the human analog of cat PGO waves.
10. See Hobson's book (80) for a excellent account of the historical foundations of dream science, as well as a description of his "Activation-Synthesis" hypothesis of dreaming based on the phasic activity of the reticular formation. Mamelak & Hobson state: "By using the term random [REM sleep neural activity] we mean to denote its spontaneous, sporadic, and automatic character. (81; p.218)." In fact, spontaneous activity has fractal patterns ove r many times scales.
11. The following description of clinical use is based on an article by H.S. Lotsof which appeared in the Winter 1994 MAPS newsletter (the author has not witnessed or experienced this treatment procedure).
12. This idea is complete spectulation, however see this Scientic American artical by Andrei Linde (The Self Reproducing Inflationary Universe) Nov 1994 (p48-55) for a good discription of fractal hyperspaces.
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