Articles and methods for simulating a psychedelic experience

Abstract

Provided herein is a method of generating a mixed reality induced psychedelic experience. The method includes providing a visual and audio output device, providing a visual and audio input, modifying at least one visual and / or auditory element of the visual and audio input, generating a modified output, and outputting the modified output to a subject through the visual and audio output device, where the modified output creates a mixed reality designed to induce a psychedelic effect, therapeutic effect, or combination thereof in the subject.

Description

Attorney Docket No. 047162-7539WO1 (02752)ARTICLES AND METHODS FOR SIMULATING A PSYCHEDELIC EXPERIENCECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority under 35 U.S.C. § 119(e) to U.S.Provisional Patent Application No. 63 / 727,963, filed December 4, 2024, which application is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION

[0002] Depression affects over 21 million people in the US, about 7 million of which have treatment resistant depression (TRD). Psychedelic medications are promising new treatments for TRD. However, their side effects and high costs of treatment prevent their widespread clinical use.

[0003] Accordingly, there remains a need in the art for articles and methods that improve upon existing articles and methods for treating TRD. The present disclosure meets this need.SUMMARY

[0004] In one aspect, a method of generating a mixed reality induced psychedelic experience includes providing a visual and audio output device; providing a visual and audio input; modifying at least one visual and / or auditory element of the visual and audio input, generating a modified output; and outputting the modified output to a subject through the visual and audio output device; wherein the modified output creates a mixed reality designed to induce a psychedelic effect, therapeutic effect, or combination thereof in the subject. In some embodiments, the modifying step includes applying one or more video and / or audio filters to the visual and audio input. In some embodiments, the modifying step is performed in real time.

[0005] In some embodiments, the modifying step includes one or more visual element modifications selected from the group comprising image stability, sharpness, color, color intensity, contrast, frame rate, movement in the field, change in depth perception, pop, flickering of lights, and combinations thereof. In some embodiments, one or more of the visual elements are differently modified between visual hemifields.

[0006] In some embodiments, the modifying step includes one or more auditory element modifications selected from the group comprising sharpness, tone, depth of sound, frequency,Attorney Docket No. 047162-7539WO1 (02752) enhanced background sounds, noise cancellation, auditory pulses, and combinations thereof. In some embodiments, one or more of the auditory elements are different modified between ears.

[0007] In some embodiments, the modifying step includes cross-modality modification. In some embodiments, the cross-modality modification includes desynchronization of audiovideo stimuli.

[0008] In some embodiments, the mixed reality is designed to induce a unique psychedelic experience. In some embodiments, the mixed reality is designed to induce a psychedelic experience that simulates a drug-induced psychedelic experience. In some embodiments, the drug-induced psychedelic experience includes ketamine, esketamine, DMT, MDMA, psilocybin, or Salvinorin A. In some embodiments, the mixed reality is designed to induce a specific therapeutic effect.

[0009] In some embodiments, the mixed reality is modified in real time. In some embodiments, the real-time modification of the mixed reality is based upon one or more responses from the subject. In some embodiments, the one or more responses are selected from the group including subjective effects, objective measures, patient demographics and characteristics, patient pretreatment mood / anxiety or other symptoms that are being targeted, patient improvement in symptoms, physiological parameters, or a combination thereof. In some embodiments, the objective measures include at least one of cardiac activity, skin conductance, encephalography (EEG), rating scales for symptom measurement, actigraphy and other sleep assessments, neuroimaging correlates of symptoms and functioning, or a combination thereof.

[0010] In some embodiments, the mixed reality is modified in real-time based upon a power spectral density (PSD) exponent ( / ) of the EEG measured from the subject. In some embodiments, modifying the mixed reality includes defining a target range forat each time step, comparing a current / (t) to the target range; computing an error term e(t) based upon the comparison of the current / (t) to the target range; and adjusting one or more elements of the mixed reality experience to reduce |e(t)|. In some embodiments, the modifying steps are repeated continuously to tune the mixed-reality experience and keep / (t) within the target range.

[0011] In some embodiments, the method further comprises executing an algorithm to adjust one or more of the elements to reduce | e(t) | . In some embodiments, the algorithm is trained to map each combination of elements to a resulting change in / . In some embodiments, the algorithm is configured to reduce |e(t) | based upon the mapped combinations of elements.Attorney Docket No. 047162-7539WO1 (02752)

[0012] In some embodiments, the real-time modification is automated, managed by an authorized individual, user managed, or a combination thereof.

[0013] In some embodiments, the method further comprises a headset including the visual and audio output device and a visual and audio input device.

[0014] In some embodiments, the method further comprises administering the mixed reality to treat depression in the subject.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] For a fuller understanding of the nature and desired objects of the present invention, reference is made to the following detailed description taken in conjunction with the accompanying drawing figures wherein like reference characters denote corresponding parts throughout the several views.

[0016] FIG. 1 shows examples of an original image and modified versions of the image. The top panel is the original image, the bottom left panel is a representation of a psychedelic drug induced modification of the original image, the bottom middle panel is a representation of a traditional virtual reality (VR) modified image, and the bottom right panel is a representation of a mixed reality version of the image according to an embodiment of the disclosure.

[0017] FIG. 2 shows a schematic illustrating a method of administering the mixed reality induced psychedelic experience according to an embodiment of the disclosure.

[0018] FIG. 3 shows a graph illustrating resting state EEG before and after the mixed reality induced psychedelic experience according to an embodiment of the disclosure.

[0019] FIG. 4 shows graphs illustrating the power spectral density (PSD) exponent derived from EEG signals.

[0020] FIGS. 5A-C show graphs illustrating association of X with cortical excitation.(A) Excitation. (B) Balance. (C) Inhibition.

[0021] FIG. 6 shows a graph illustrating the changes in x during and after a simulated psychedelic experience according to an embodiment described herein.

[0022] FIGS. 7A-B show graphs illustrating association between changes in x and reductions in anxiety and restlessness. (A) Anxiety reduction. (B) Restlessness reduction.

[0023] FIGS. 8A-B show graphs illustrating association between changes in x and increases in energy and relaxation. (A) Energy increase. (B) Relaxation increase.Attorney Docket No. 047162-7539WO1 (02752)DETAILED DESCRIPTIONDefinitions

[0024] As used herein, each of the following terms has the meaning associated with it in this section. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Generally, the nomenclature used herein and the laboratory procedures in molecular biology, immunology, animal pharmacology, pharmaceutical science, peptide chemistry, and organic chemistry are those well-known and commonly employed in the art. It should be understood that the order of steps or order for performing certain actions is immaterial, so long as the present teachings remain operable. Any use of section headings is intended to aid reading of the document and is not to be interpreted as limiting; information that is relevant to a section heading may occur within or outside of that particular section. All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference.

[0025] In the application, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components and can be selected from a group consisting of two or more of the recited elements or components.

[0026] In the methods described herein, the acts can be carried out in any order, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed act of doing X and a claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process.

[0027] As used herein, the singular form “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

[0028] Unless specifically stated or obvious from context, as used herein, the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. “About” can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about.Attorney Docket No. 047162-7539WO1 (02752)

[0029] As used herein, the terms “comprises,” “comprising,” “containing,” “having,” and the like can have the meaning ascribed to them in U.S. patent law and can mean “includes,” “including,” and the like.

[0030] Unless specifically stated or obvious from context, the term “or,” as used herein, is understood to be inclusive.

[0031] Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 (as well as fractions thereof unless the context clearly dictates otherwise).

[0032] As used herein, the term “ratio” refers to a relationship between two numbers (e.g., scores, summations, and the like). Although, ratios can be expressed in a particular order (e. , a to b or tzA), one of ordinary skill in the art will recognize that the underlying relationship between the numbers can be expressed in any order without losing the significance of the underlying relationship, although observation and correlation of trends based on the ration may need to be reversed. For example, if the values of a over time are (4, 10) and the values of b over time are (2, 4), the ratio c .b will equal (2, 2.5), while the ratio b a will be (0.5, 0.4). Although the values of a and b are the same in both ratios, the ratios cr.b and b a are inverse and increase and decrease, respectively, over the time period.Detailed Description

[0033] Provided herein are methods of generating a mixed reality induced psychedelic experience. In some embodiments, the method includes providing a visual output device and / or audio output device, providing a visual and / or audio input, modifying at least one visual and / or auditory element of the visual and / or audio input, and outputting the modified visual and / or audio input to a subject through the visual output device and / or audio output device. At least one visual and / or auditory element is modified through any suitable manner, such as, but not limited to, using one or more video and / or audio filters applied to the visual and / or audio input.

[0034] The visual output device includes any suitable device for displaying modified visual images to a subject, such as, but not limited to, glasses, goggles, immersive wearable devices, screens, any other suitable visual display, or combinations thereof. In someAttorney Docket No. 047162-7539WO1 (02752) embodiments, the visual output device delivers the modified visual images to each visual hemifield independently. The audio output device includes any suitable devices for outputting modified audio to a subject, such as, but not limited to, ear buds, headphones, any other suitable speaker, or combinations thereof. In some embodiments, the audio output device delivers the modified audio to each ear individually. In some embodiments, the visual and audio output devices are combined in a single device, such as, but not limited to, immersive goggles with built-in speakers. In some embodiments, the visual and / or audio output device supports, creates, and / or provides a three-dimensional (3D) visual and / or auditory output.

[0035] The visual and / or audio input includes any suitable visual and / or audio input for generating a mixed reality experience. In some embodiments, for example, the visual and / or audio input includes pre-recorded video and / or audio that may be familiar or new to the subject. Additionally or alternatively, in some embodiments, the video and / or audio is captured by a video and / or audio input device. In some such embodiments, the method includes generating the mixed reality in real time as the video and / or audio is captured by the input device(s). For example, in one embodiment, the method includes capturing video and / or audio with the input device(s), modifying at least one visual and / or auditory element of the video and / or audio as it is captured, and outputting the modified video and / or audio to the subject in real time (z.c., modifying / morphing the real environment of the subject). Suitable input devices include, but are not limited to, a camera and / or microphone. In some embodiments, the input device(s) are integral with the output device(s), such as, but not limited to, a headset providing raw camera access.

[0036] The mixed reality induced psychedelic experience described herein is designed to provide a psychedelic effect, a therapeutic effect, or both. For example, in some embodiments, the method includes modifying one or more visual and / or auditory elements in a manner that produces certain neurophysiological changes which promote a psychedelic effect, therapeutic effect, or both. Any visual and / or auditory element may be modified to generate a desired mixed reality induced psychedelic experience, including, but not limited to, image stability, sharpness, color, color intensity (saturation), contrast, frame rate, movement in the field, change in depth perception, pop (enhanced borders / edges), flickering of lights, any other visual element, auditory sharpness (e.g., feeling underwater), tone, depth of sound, frequency, enhanced background sounds (e.g., wave-like or whooshing sounds), noise cancellation, auditory pulses, any otherAttorney Docket No. 047162-7539WO1 (02752) auditory element, or a combination thereof. In some embodiments, one or more elements may be differently modified between visual hemifields and / or ears. Additionally, or alternatively, in some embodiments, the modifications are cross modality, such as, but not limited to, desynchronization of audio-visual stimuli. FIG. 1 shows an example of a mixed reality modified image (bottom right panel), as compared to the original image (top panel), a representation of a drug induced modification of the image (bottom left panel), and a traditional virtual reality (VR) modified version of the image (bottom middle panel). As will be appreciated by those skilled in the art, any specific combination of modified visual and / or auditory elements can be selected to induce any desired psychedelic experience.

[0037] In some embodiments, the method includes modifying one or more visual and / or auditory elements to induce a specific psychedelic effect. The specific psychedelic effect can include a new and / or unique psychedelic experience (e.g., not based upon a known drug induced or other psychedelic experience), or can simulate and / or approximate a drug-induced psychedelic experience. A psychedelic experience corresponding to any psychedelic or psychoactive drug can be induced by the mixed reality generated according to one or more of the embodiments disclosed herein. In such embodiments, the method may include modifying specific visual and / or auditory elements based upon descriptions of effects and experiences, measured brain effects, and / or biomarkers (e.g, measured psychological effects) from the corresponding psychedelic or psychoactive substance. For example, in some embodiments, the method includes modifying image stability, sharpness, color, color intensity (saturation), contrast, frame rate, movement in the field, change in depth perception, pop (enhanced borders / edges), flickering of lights, any other visual element, auditory sharpness (e.g., feeling underwater), tone, depth of sound, frequency, enhanced background sounds (e.g., wave-like or whooshing sounds), noise cancellation, auditory pulses, any other auditory element, or a combination thereof to generate a mixed reality induced psychedelic experience simulating and / or approximating a desired drug- induced psychedelic experience. In some embodiments, for example, the desired drug-induced psychedelic experience simulates and / or approximates a ketamine induced psychedelic experience. Other examples of specific drug induced psychedelic experiences include, but are not limited to, esketamine, DMT, MDMA, psilocybin, and / or Salvinorin A.

[0038] In some embodiments, the same or similar visual and / or auditory elements are modified, only in different proportions, in order to simulate different drug-induced psychedelicAttorney Docket No. 047162-7539WO1 (02752) experiences. For example, in some embodiments, simulating a ketamine-induced psychedelic experience includes modifying depth of perception and illusion of motion of visual stimuli. In some embodiments, simulating a psilocybin-induced psychedelic experience includes modifying the color and contrast of visual stimuli. In some embodiments, simulating psychedelic experiences not necessarily related to one drug, includes modifying the loudness, clarity and dissonance of auditory stimuli and passage of time. Although described herein with respect to specific examples, as will be appreciated by those skilled in the art, the disclosure is not so limited and expressly includes modifying any combination of visual and / or auditory elements to generate any desired mixed reality induced psychedelic experience.

[0039] By modifying one or more visual and / or auditory elements to induce a specific psychedelic effect in a subject, as described herein, the present methods produce measurable effects in the subject. These effects include both objective effects and subjective effects. For example, in some embodiments, inducing the specific psychedelic effect reduces the slope of the power spectral density (PSD) curve in measured electroencephalography (EEG) during the simulated experience, which is captured as a reduction in the exponent ( ) of the power-law relationship between PSD and frequency (PSD In some embodiments, the change in / persists, or is maintained, after the simulated experience, establishing a lasting effect on the subject. In some embodiments, a reduction in / correlates with subjective effects, including, but not limited to, reduced anxiety, reduced restlessness, increased energy, and / or increased relaxation, during and / or after the simulated experience.

[0040] Additionally or alternatively, in some embodiments, the method includes modifying one or more visual and / or auditory elements to induce a specific therapeutic effect. For example, in some embodiments, modifying one or more visual and / or auditory elements to induce a specific therapeutic effect includes simulating and / or approximating a drug-induced psychedelic experience in order to provide a therapeutic effect associated with that drug-induced psychedelic experience. In such embodiments, one or more visual and / or auditory elements can be additionally or further modified to change, combine, and / or enhance the therapeutic effect associated with the specific drug-induced psychedelic experience. Alternatively, in some embodiments, the method includes modifying one or more visual and / or auditory elements to induce a specific therapeutic effect without simulating and / or approximating any specific drug- induced psychedelic experience (e.g, inducing a new / unique psychedelic experience directed toAttorney Docket No. 047162-7539WO1 (02752) providing specific therapeutic effects). An example of the process for administering the mixed reality to induce a specific therapeutic effect is illustrated in FIG. 2.

[0041] In some embodiments, the method includes modifying the mixed reality induced psychedelic experience in real time. The real-time modification of the mixed reality induced psychedelic experience can be automated, managed by an authorized individual (e. ., a clinician or operator-managed platform), user managed (e.g., the ability to “tune” specific components of the experience to hone in on a specific experience), or a combination thereof. In some embodiments, the real-time modification is based upon one or more responses from the subject. Suitable responses include, but are not limited to, subjective effects (e.g., feedback from the subject relating to comfort, perceived experience, or other subjective information) and / or objective measures (e.g., cardiac activity, skin conductance, other psychophysiological information, electroencephalography (EEG), rating scales for symptom measurement, actigraphy and other sleep assessments, neuroimaging correlates of symptoms and functioning, etc.). The real-time modification may also factor in other parameters, such as, but not limited to, patient demographics (e.g., age, gender, etc.) and characteristics; patient’s pre-treatment mood / anxiety or other symptoms that are being targeted; patients improvement in symptoms; physiological parameters (e.g., sleep, appetite, gastrointestinal and sympathetic nervous system functioning, etc.), or a combination thereof. For example, in some embodiments, the method includes receiving feedback from the subject and modifying one or more elements of the mixed reality in real-time based upon the feedback. Accordingly, in some embodiments, the method includes generating an interactive mixed reality induced psychedelic experience.

[0042] Additionally or alternatively, in some embodiments, the method includes measuring EEG from the subject during the mixed reality induced psychedelic experience and modifying one or more elements of the mixed reality in real-time based upon the measured EEG. In some such embodiments, the EEG recorded from the subject during the mixed reality induced psychedelic experience is compared against benchmark EEG levels, and one or more elements are modified based upon differences between the EEG from the subject and the benchmark EEG levels. Suitable benchmarks include, but are not limited to, baseline EEG from the subject, EEG recordings from corresponding drug induced psychedelic experiences, any other suitable benchmark to inform and / or quantify the subjects response to the mixed reality, or a combination thereof. In some embodiments, the method includes modifying one or more elements of theAttorney Docket No. 047162-7539WO1 (02752) mixed reality in real-time based upon the power spectral density (PSD) exponent t / ) of the measured EEG. For example, in some embodiments, the method includes defining a target range for / ; at each time step, comparing the current / (t) to the target range; computing an error term e(t) based upon the comparison of the current / (t) to the target range; and adjusting one or more of the elements to reduce | e(t) | . This process can be repeated continuously to tune the mixed-reality experience and keep / (t) within the desired target range.

[0043] In some embodiments, the method includes executing an algorithm to adjust one or more of the elements to reduce |e(t) |. In some such embodiments, the method further includes training the algorithm. For example, in some embodiments, the method includes training the algorithm to map each combination of elements (filter combination) to a resulting change (increase / decrease) in / . Based upon this mapping, the filter can be adjusted to provide the desired reduction in |e(t)|. The algorithm can be trained in any suitable manner, including, but not limited to, using training datasets comprising EEG recordings collected during known psychedelic or altered-state experiences; EEG recordings obtained during mixed-reality sessions with predefined filter and element combinations; or any combination thereof. Training can include pre-processing steps such as filtering, artifact removal, segmentation, or feature extraction (e.g., PSD estimation, ^-tracking). The algorithm may be trained using supervised learning, unsupervised learning, self-supervised learning, reinforcement learning, or guided adjustment procedures in which human evaluators provide labels or reward signals. In some embodiments, the algorithm is further refined using adaptive or online updates based on realtime EEG measurements from the subject.

[0044] In some embodiments, unlike with a drug that produces “all or nothing” psychedelic effects in several domains (color, brightness, shapes, depth, sharpness of image, clarity of sounds, echo, etc), the current methods permit / include obtaining a “signature” for each effect separately and / or a “signature” for the cumulative simulated psychedelic effects. Additionally or alternatively, in some embodiments, the method includes collecting effects on mood, stress, comfort, as well as clinical outcomes, EEG, and psychophysiological data before and after each mixed reality induced psychedelic experience. In some embodiments, the method includes generating a pattern of long-term effects from the collected data. In some embodiments, the collected data (e.g., simulation metrics, subjective responses, pre-treatment psychophysiological and EEG responses, and clinical outcome measures) inform a feedbackAttorney Docket No. 047162-7539WO1 (02752) algorithm for simulation development to identify and streamline the pattern of effects that produce a range of psychedelic effects with refined intensity, tolerability, therapeutic efficacy, and feasibility. In some embodiments, the method includes isolating certain types of psychedelic effects based upon the collected data to predict psychedelic experience and therapeutic responses.

[0045] In contrast to traditional virtual reality methods, where the goal is to produce a calming environment to make drug-induced psychedelic experiences better, the methods disclosed herein provide mixed reality induced perceptual alterations that mimic psychedelic experiences (i.e., non-drug-induced simulations of psychedelic experiences). By inducing the psychedelic experiences without administering the corresponding psychedelic drug, the methods according to the embodiments disclosed herein eliminate the medication related challenges associated with psychedelic treatment. As such, the methods disclosed herein provide a new psychedelic treatment for various conditions, such as, but not limited to, depression, major depressive disorder (MDD), treatment resistant depression (TRD), or any other condition where psychedelic treatment would be beneficial. Additionally or alternatively, the methods according to one or more of the embodiments disclosed herein can serve as an educational tool and / or support research studies of psychedelic drugs. Alternatively, in some embodiments, the mixed reality disclosed herein can be combined with administration of a reduced dose of a psychedelic or psychoactive drug while achieving the same effects as a full dose of the psychedelic or psychoactive drug, thus making the drug treatment safer.

[0046] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents were considered to be within the scope of this invention and covered by the claims appended hereto.

[0047] It is to be understood that wherever values and ranges are provided herein, all values and ranges encompassed by these values and ranges, are meant to be encompassed within the scope of the present invention. Moreover, all values that fall within these ranges, as well as the upper or lower limits of a range of values, are also contemplated by the present application.

[0048] The following examples further illustrate aspects of the present invention. However, they are in no way a limitation of the teachings or disclosure of the present invention as set forth herein.Attorney Docket No. 047162-7539WO1 (02752)EXAMPLESEXAMPLE 1

[0049] The mixed reality induced psychedelic experience according to one or more of the embodiments disclosed herein was administered to a subject. Resting state EEG was measured from the subject before and after administering the mixed reality induced psychedelic experience. As illustrated in FIG. 3, the resting state EEG was shifted following the mixed reality induced psychedelic experience. This shift was similar to that observed with psychedelic drugs, showing that the mixed reality induced psychedelic experience produces similar effects.EXAMPLE 2 - PSD in Simulated Ketamine Experience

[0050] There is a decaying power-law relationship between power spectral density (PSD) and frequency in EEG signals, which can be parameterized with a positive exponent X (FIG. 4). As illustrated in FIGS. 5A-C, x can be used to track changes in cortical dynamics, where reductions in x are associated with cortical excitation.

[0051] Turning to FIG. 6, a simulated ketamine-induced psychedelic experience provided by the methods described herein reduces x inEEG signals measured from the subject. This reduction in x provided by the simulated experience is similar to that provided by ketamine, and persists after the simulated experience has concluded (FIG. 6). In addition, the changes in x provided by the simulated experience correlate with subjective changes, such as reductions in anxiety and restlessness (FIGS. 7A-B) and increases in energy and relaxation (FIGS. 8A-B).EQUIVALENTS

[0052] Although preferred embodiments of the invention have been described using specific terms, such description is for illustrative purposes only, and it is to be understood that changes and variations may be made without departing from the spirit or scope of the following claims.INCORPORATION BY REFERENCE

[0053] The entire contents of all patents, published patent applications, and other references cited herein are hereby expressly incorporated herein in their entireties by reference.

Claims

Attomey Docket No. 047162-7539WO1 (02752)CLAIMSWhat is claimed is:

1. A method of generating a mixed reality induced psychedelic experience, the method comprising: providing a visual and audio output device; providing a visual and audio input; modifying at least one visual and / or auditory element of the visual and audio input, generating a modified output; and outputting the modified output to a subject through the visual and audio output device; wherein the modified output creates a mixed reality designed to induce a psychedelic effect, therapeutic effect, or combination thereof in the subject.

2. The method of claim 1, wherein the modifying step includes applying one or more video and / or audio filters to the visual and audio input.

3. The method of claim 1, wherein the modifying step is performed in real time.

4. The method of claim 1, wherein the modifying step includes one or more visual element modifications selected from the group comprising image stability, sharpness, color, color intensity, contrast, frame rate, movement in the field, change in depth perception, pop, flickering of lights, and combinations thereof.

5. The method of claim 4, wherein one or more of the visual elements are differently modified between visual hemifields.

6. The method of claim 1, wherein the modifying step includes one or more auditory element modifications selected from the group comprising sharpness, tone, depth of sound, frequency, enhanced background sounds, noise cancellation, auditory pulses, and combinations thereof.

7. The method of claim 6, wherein one or more of the auditory elements are different modified between ears.Attomey Docket No. 047162-7539WO1 (02752)8. The method of claim 1, wherein the modifying step includes cross-modality modification.

9. The method of claim 8, wherein the cross-modality modification includes desynchronization of audio-video stimuli.

10. The method of claim 1, wherein the mixed reality is designed to induce a unique psychedelic experience.

11. The method of claim 1, wherein the mixed reality is designed to induce a psychedelic experience that simulates a drug-induced psychedelic experience.

12. The method of claim 11, wherein the drug-induced psychedelic experience includes ketamine, esketamine, DMT, MDMA, psilocybin, or Salvinorin A.

13. The method of claim 1, wherein the mixed reality is designed to induce a specific therapeutic effect.

14. The method of claim 1, wherein the mixed reality is modified in real time.

15. The method of claim 14, wherein the real-time modification of the mixed reality is based upon one or more responses from the subject.

16. The method of claim 15, wherein the one or more responses are selected from the group including subjective effects, objective measures, patient demographics and characteristics, patient pretreatment mood / anxiety or other symptoms that are being targeted, patient improvement in symptoms, physiological parameters, or a combination thereof.

17. The method of claim 16, wherein the objective measures include at least one of cardiac activity, skin conductance, encephalography (EEG), rating scales for symptom measurement, actigraphy and other sleep assessments, neuroimaging correlates of symptoms and functioning, or a combination thereof.

18. The method of claim 17, wherein the mixed reality is modified in real-time based upon a power spectral density (PSD) exponent (x) of the EEG measured from the subject.

19. The method of claim 18, wherein modifying the mixed reality includes:Attomey Docket No. 047162-7539WO1 (02752) defining a target range for / ; at each time step, comparing a current / (t) to the target range; computing an error term e(t) based upon the comparison of the current / (t) to the target range; and adjusting one or more elements of the mixed reality experience to reduce | e(t) | .

20. The method of claim 19, wherein the modifying steps are repeated continuously to tune the mixed-reality experience and keep / (t) within the target range.

21. The method of claim 19, further comprising executing an algorithm to adjust one or more of the elements to reduce | e(t) | .

22. The method of claim 21, wherein the algorithm is trained to map each combination of elements to a resulting change in / .

23. The method of claim 22, wherein the algorithm is configured to reduce |e(t) | based upon the mapped combinations of elements.

24. The method of claim 14, wherein the real-time modification is automated, managed by an authorized individual, user managed, or a combination thereof.

25. The method of claim 1, further comprising a headset including the visual and audio output device and a visual and audio input device.

26. The method of claim 1, further comprising administering the mixed reality to treat depression in the subject.

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