Exhibit 99.1

Zynerba Pharmaceuticals Reports Fourth Quarter and Full Year 2022 Financial Results and Operational Highlights

Enrollment continues in RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel™ in patients with Fragile X syndrome; topline results expected first-half 2024

European Commission granted orphan drug designation for cannabidiol, the active ingredient in Zygel, in 22q11.2 deletion syndrome

$50.6 million in cash and cash equivalents at December 31, 2022; Cash runway to mid-year 2024

DEVON, Pa., March 28, 2023 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today reported financial results for the fourth quarter and full year ended December 31, 2022, and provided an overview of recent operational highlights and a pipeline update.

“We remain focused on enrolling patients in our confirmatory pivotal Phase 3 RECONNECT trial, and expect topline results in the first half of 2024,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We are committed to bringing the first pharmaceutical product indicated for the treatment of behavioral symptoms of Fragile X syndrome to market, and with a cash runway to mid-year 2024, we remain well-positioned on achieving that goal.”

Operational Highlights and Pipeline Update

Zygel in Fragile X Syndrome (FXS)

Zygel in 22q11.2 Deletion Syndrome (22q)

Fourth Quarter and Full Year 2022 Financial Results

Research and development expenses were $5.5 million for the fourth quarter of 2022, including stock-based compensation of $0.5 million. General and administrative expenses were $3.2 million in the fourth quarter of 2022, including stock-based compensation expense of $0.5 million. Net loss for the fourth quarter of 2022 was $8.0 million, with basic and diluted loss per share of $(0.18).

Research and development expenses were $21.1 million for full year 2022, including stock-based compensation of $2.0 million. General and administrative expenses were $14.2 million for full year 2022, including stock-based compensation expense of $2.4 million. Net loss for full year 2022 was $35.0 million, with basic and diluted loss per share of $(0.82).

Financial Outlook

As of December 31, 2022, cash and cash equivalents were $50.6 million, compared to $67.8 million as of December 31, 2021. On March 13, 2023, the Company issued a statement confirming that it does not hold cash deposits or securities at Silicon Valley Bank.

On May 11, 2021, the Company entered into a Controlled Equity Offering^SM Sales Agreement (2021 Sales Agreement), with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc., as sales agents, pursuant to which the Company may sell, from time to time, up to $75.0 million of its common stock. During the year ended December 31, 2022, the Company sold and issued 4,608,274 shares of its common stock under the 2021 Sales Agreement in the open market resulting in gross proceeds of $6.2 million and net proceeds of $5.8 million, after deducting commissions and offering expenses. From January 1, 2023 through March 22, 2023, the Company sold and issued 1,179,077 shares of its common stock under the 2021 Sales Agreement in the open market resulting in gross proceeds of $0.7 million and net proceeds of $0.6 million, after deducting commissions and offering expenses.

On July 21, 2022, the Company entered into a Purchase Agreement and registration rights agreement for up to $20 million with Lincoln Park Capital Fund, LLC (LPC), a Chicago-based institutional investor. During the year ended December 31, 2022, the Company sold and issued 350,000 shares of its common stock under the 2022 Purchase Agreement with LPC in the open market resulting in gross proceeds of $0.3 million and net proceeds of $0.2 million, after deducting offering expenses. From January 1, 2023 through March 22, 2023, the Company sold and issued 1,950,000 shares of its common stock under the Purchase Agreement, resulting in gross and net proceeds of $1.0 million.

Management believes that the Company’s cash and cash equivalents are sufficient to fund operations and capital requirements into mid-year 2024. Top-line results from the Company’s confirmatory pivotal Phase 3 RECONNECT trial of Zygel in patients with FXS are expected in the first half of 2024.

About Zygel

Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba Contacts

Jim Fickenscher, CFO and VP Corporate Development 

Zynerba Pharmaceuticals 

484.581.7483 

fickenscherj@zynerba.com

Peter Vozzo 

ICR Westwicke 

Office: 443.213.0505 

Cell: 443.377.4767 

Peter.Vozzo@Westwicke.com

Exhibit 99.2

© 2022 Zynerba Pharmaceuticals, Inc. All rights reserved. NASDAQ ZYNE Advancing Science. Improving Connections. Next - Generation Transdermal Cannabinoid Therapeutics March 2023

Forward - Looking Statements The statements in this presentation may include forward - looking statements within the meaning of the private securities litigati on reform act of 1995. These statements, among other things relate to the future operations, opportunities, or financial performance of Zy nerba Pharmaceuticals, Inc. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “ est imates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” or other words that convey uncertain ty of future events or outcomes to identify these forward - looking statements. Such statements are subject to numerous important factors, risks and unce rtainties that may cause actual events or results to differ materially from the Company’s current expectations, including but not limited to the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticip ate d; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relatin g t o enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in the C omp any’s ongoing or planned clinical trials in FXS, 22q, or in any additional trials, and may not otherwise support further development in a s pec ified indication or at all; the Company’s RECONNECT trial may not be determined to be sufficient to support a submission for regulatory approv al, including an NDA or MAA; actions or advice of the U.S. Food and Drug Administration or foreign regulatory agencies may affect th e design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Co mpany’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s e xpe ctations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidate s; the extent to which health epidemics or other outbreaks of communicable diseases, including COVID - 19, could disrupt our operations or adversel y affect our business and financial conditions; and the extent to which inflation or global instability, including political in sta bility, may disrupt our business operations or our financial condition. These and other risks are described in our filings with the U.S. Securities and Exchange Commission, available at www.sec.gov. Any forward - looking statements that the Company makes in this presentation speak only as o f the date of this presentation. The Company assumes no obligation to update forward - looking statements whether as a result of new information, future events or otherwise, after the date of this presentation . March 2023 Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 2 © 2022 Zynerba Pharmaceuticals, Inc. All rights reserved. Zynerba and Zygel are trademarks of Zynerba Pharmaceuticals, Inc. A ll other trademarks are property of their respective owners.

A different and exciting approach to Cannabidiol

An Orphan - Focused Neuropsychiatric, Biopharmaceutical Company Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 4 Permeation - enhanced Patent - protected through 2040 Pharmaceutically manufactured; THC free FIRST AND ONLY TRANSDERMAL CANNABIDIOL GEL One Phase 3 clinical program ongoing One additional orphan indication is Phase 3 ready LATE - STAGE PIPELINE Leadership expertise in transdermal delivery, rare diseases and specialty markets Clean balance sheet and cash runway to mid - year 2024 POSITIONED FOR SUCCESS A different and exciting approach to Cannabidiol March 2023

Benefits of Our Approach to Cannabidiol Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 5 FDA regulated Consistency of production Purity of ingredients No THC – not a scheduled drug by U.S. DEA Scalable production process PHARMACEUTICAL MANUFACTURING PHARMACEUTICAL DISPENSARY Ease of application for caregivers of patients with behavioral issues Minimizes GI side effects and reduces risk for liver toxicity Lower risk for drug/drug interactions Avoids conversion to THC in stomach Provides cannabidiol plasma levels similar to oral cannabidiol (5 - 10 mg/ kg) plasma levels TRANSDERMAL DELIVERY March 2023

• Cannabidiol pre - dose concentrations in adults with epilepsy receiving either 195 mg/day or 390 mg/day of Zygel ranged from 0.72 ng/mL to 77.50 ng/mL • Cannabidiol pre - dose concentrations peaked at 235 ng/mL in adults who received Zygel in doses ranging from 390 mg/day to 780 mg/day in the open - label extension phase of the trial • The concentrations achieved overlap those reported with oral cannabidiol (5 - 10 mg/kg/day) • Consistent with trials of oral cannabidiol, substantial variation in interindividual and intraindividual plasma concentrations was reported • THC was not detected in the plasma Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 6 Transdermal Administration of Cannabidiol Successfully Achieved Plasma Concentrations that Overlap Those Reported with Oral Cannabidiol (5 - 10mg/kg) Source: O’Brien TJ et al. JAMA Netw Open. 2022;5(7):e2220189. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794028 March 2023

Clinical Development Programs Fragile X Syndrome FXS 22q Deletion Syndrome 22q

Overlap of Symptoms Across Conditions Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 8 Anxiety Seeks Isolation Social Avoidance Lack of Interaction Attention Deficits Irritability FXS 22q March 2023

Fragile X Syndrome (FXS) Focused Clinical Pipeline Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 9 Preclinical Phase 1 Phase 2 Pivotal Market 22q Deletion Syndrome (22q) Regulatory Filing U.S. Orphan Drug and Fast Track designations; EU Orphan Drug designation U.S. Orphan Drug designation; EU Orphan Drug designation Zygel TM (ZYN002 Cannabidiol Gel) March 2023

• Zygel safety database across all clinical studies includes data from over 900 volunteers and patients • Majority of treatment - emergent AEs (TEAEs) were mild or moderate • Most common Zygel - related TEAEs were application site events, the majority of which were mild and transient • No clinically significant changes in vital signs or ECGs • No Zygel - related clinically significant changes in laboratory values, including liver function tests Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 10 Well - Tolerated Safety Profile March 2023

Fragile X Syndrome

~78K U.S. PATIENTS What is Fragile X Syndrome (FXS)? Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 12 • Leading known cause of inherited intellectual disability and autism spectrum disorder • Mutation of the FMR1 gene causes endocannabinoid system (ECS) dysregulation • Easily identified mutation manifests as multiple CGG repeats on FMR1 (full mutation >200 repeats) • Resulting in cognitive, social, and behavioral symptoms • Behavioral Symptoms linked to deficiencies in the ECS WITH FXS EU/UK PATIENTS ~121K U.S. & EU Orphan Drug Designation Granted for FXS March 2023

Poised for Success in FXS Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 13 Largest clinical trial ever conducted in children with FXS Extensive safety database Patients on drug for up to five years Statistically significant outcomes in children with complete methylation Lessons Learned from Previous Trials Improve Probability of Success in RECONNECT Pivotal Trial March 2023

Role of FMR1 Methylation in FXS Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 14 • FMR1 gene codes for production of FMRP* which is vital to synapse development • Methylation of the FMR1 gene plays a role in determining gene function • When methylation of the FMR1 gene silences the gene, no FMRP is produced: • Systems and processes affected by FMRP become dysregulated • ~60% of FXS patients are believed to be completely methylated • Completely methylated patients are the most severely impacted ~47K U.S. PATIENTS WITH COMPLETE METHYLATION EU/UK PATIENTS ~73K *RNA - binding protein that helps regulate synaptic development and plasticity March 2023

CONNECT - FX Trial Key Learning: Results with complete methylation of FMR1 gene Consistent Improvements Observed with Zygel vs. Placebo in Patients with Complete Methylation Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 15 PRIMARY ENDPOINT CAREGIVER REPORTED BEHAVIOR CHANGE CLINICIAN REPORTED BEHAVIOR IMPROVEMENTS CLINICALLY MEANINGFUL BEHAVIOR IMPROVEMENTS ABC - C FXS Social Avoidance Subscale Caregiver Global Impression of Change (ZYGEL vs Placebo) Clinical Global Impression of Improvement (anchored)** More Patients Achieved Meaningful Change (ZYGEL vs Placebo) Ad hoc analysis of 136 patients with complete methylation *Statistically significant , ** Not specific to Social Avoidance 40% median percent improvement in socially avoidant behaviors ( p =0.027*) SOCIAL INTERACTION 63% vs 37% ( p =0.005*) IRRITABLE/DISRUPTIVE BEHAVIORS 54% vs 33% ( p =0.027*) SOCIAL AVOIDANCE/ISOLATION 58% vs 46% ( p =0.195) OVERALL BEHAVIOR 61% vs 46% ( p =0.100) ANY IMPROVEMENT Zygel vs placebo 50% vs 36% ( p =0.128) SOCIAL AVOIDANCE (≥ 3 POINTS) 56% vs 37% ( p =0.030*) IRRITABILITY (≥ 9 POINTS) 37% vs 26% ( p =0.232) March 2023

Sustained Improvement in Patients With Complete Methylation of FMR1 a a. Patients matching primary efficacy population in RECONNECT. b. ZYN2 - CL - 016 (CONNECT - FX). c. Least square mean ± SE; reduction equals improvement. -6 -5 -4 -3 -2 -1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Change from baseline c Placebo (n) Zygel (n) 48 47 47 45 49 46 45 43 43 44 36 40 31 33 31 33 Zygel Placebo Switch from Placebo to Zygel Month Change in ABC - C FXS Social Avoidance Open - Label Extension Patients on Zygel Œ CONNECT - FX Double - Blind c Zynerba Pharmaceuticals | Advancing Science. Improving Connections. RECONNECT Population Continued improvement through 4 months used to support increasing treatment period in RECONNECT to 4 months March 2023 16

Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 17 Clinically Meaningful Improvement a Achieved and Maintained in Patients with Complete Methylation b 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Cumulative Percentage of Patients Month Zygel (n=47) Placebo (n=49) Switch from Placebo to Zygel CONNECT - FX Double - Blind c Open - Label Extension Patients on Zygel a. Meaningful change in Social Avoidance: ≥3 - point improvement from baseline; maintained for ≥ 2 consecutive visits b. Patients matching primary efficacy population in RECONNECT c. ZYN2 - CL - 016 (CONNECT - FX) Percentage of patients with clinically meaningful improvement in ABC - C FXS Social Avoidance March 2023 RECONNECT Population

CONNECT - FX Data Published in the Journal of Neurodevelopmental Disorders Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 18 • “…ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe.” • “Thus, CONNECT - FX appears to provide evidence that identifies a biologically identifiable and clinically responsive population of patients affected by FXS who are defined by both full mutation and ≥ 90% methylation of the FMR1 gene.” The article can be accessed online at the Journal of Neurodevelopmental Disorders at https://rdcu.be/c0sKz . J Neurodev Disord . 2022 Nov 25;14(1):56. doi : 10.1186/s11689 - 022 - 09466 - 6 March 2023

Role of Endocannabinoid System and Cannabidiol Therapy in FXS Published in the Journal of Neurodevelopmental Disorders Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 19 • “…Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS).” • “FXS is caused by deficiency or absence of FMRP [FRM1 protein]…The absence of FMRP downregulates the ECS signaling, which has been implicated in FXS pathogenesis.” • “Consistent with these proposed mechanisms of action of cannabidiol in FXS, in the CONNECT - FX trial the transdermal cannabidiol gel, ZYN002 [ Zygel Œ ], was associated with improvements in measures of social avoidance, irritability, and social interaction, particularly in patients who are most affected, showing ≥90% methylation of the FMR1 gene.” The article can be accessed online at the Journal of Neurodevelopmental Disorders at https://rdcu.be/c25fu . J Neurodev Disord. 2023 Jan 9;15(1):1. doi: 10.1186/s11689 - 023 - 09475 - z . March 2023

Design Optimized from CONNECT - FX Trial Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 20 More patient and family friendly Extending trial to 18 - weeks Increased dosing option for individuals >50 kg Successful completion of Phase 3 pivotal trial expected to satisfy requirements for an NDA submission in the U.S. and a marketing authorization application in the EU. Primary endpoint: Patients with complete methylation March 2023

Confirmatory Pivotal Trial Design Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 21 Double - Blind, Placebo - Controlled Study: Initiated 18 weeks 3 to 22 years old Moderate - to - Severe FXS Zygel (n~100; 80*) 250 mg daily (≤30kg) 500 mg daily (>30kg) 750 mg daily (>50kg) (weight - based dose) Placebo (n~100; 80*) Mirrors Zygel administration *Patients with complete methylation of FMR1 gene Patients randomized (1:1) to receive either Zygel or placebo Open Label Extension (OLE): Ongoing 24 months All patients receive Zygel March 2023

Trial Objectives Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 22 Change from baseline to end of treatment in ABC - C FXS Social Avoidance subscale in patients who have complete (100%) methylation of their FMR1 gene • Change from baseline to end of treatment in: • ABC - C FXS Irritability subscale in patients who have complete methylation • ABC - C FXS Social Avoidance subscale among all randomized patients (complete and partial methylation) • Percent of patients: • With any improvement on the Caregiver Global Impression of Change (CaGI - C) for Social Interactions among patients with complete methylation • Rated as improved on the Clinical Global Impression - Improvement (CGI - I) scale among patients with complete methylation SECONDARY ENDPOINTS PRIMARY ENDPOINT March 2023

Next Steps in FXS Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 23 Continued RECONNECT pivotal trial enrollment Topline results expected in 1H 2024 March 2023

22q11.2 Deletion Syndrome (22q) Image courtesy Positive Exposure © 2016 Positive Exposure. All rights reserved. www.PositiveExposure.org . Eliza, living with 22q11.2 deletion syndrome

What is 22q11.2 Deletion Syndrome (22q)? Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 25 • Rare disorder and second most common genetic disorder, behind Down s yndrome • Midline condition with abnormalities affecting palate, face, heart and other organs; surgically corrected in infancy • Neuropsychiatric illnesses and learning disabilities common • Early onset of neuropsychiatric symptoms disrupts development and quality of life, and heightens risk of later psychotic disorders • No drugs currently approved WITH 22q ~83K U.S. PATIENTS ~129K EU/UK PATIENTS March 2023

U.S. & EU ORPHAN DRUG DESIGNATION GRANTED FOR TREATMENT OF 22q Rationale for Zygel in 22q Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 26 • Overlapping symptoms with FXS and ASD • Associated with increased anxiety, irritability, social withdrawal and social interaction problems • Cannabidiol may treat neurop sychiatric symptoms due to activity as: • Modulator of ECS • Agonist at serotonin 1A receptors • Antagonist at GPR55 receptors March 2023

INSPIRE Phase 2 Trial Design Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 27 Period 1: Completed 14 weeks 4 to 15 years old With 22q11.2 Deletion Syndrome Zygel (n = 20) 250 mg daily (≤35kg) 500 mg daily (>35kg) (weight - based dose) Period 2: Completed 24 weeks Efficacy assessments include: (week 14 vs baseline) • Anxiety, Depression and Mood Scale (ADAMS) • Aberrant Behavior Checklist - Community (ABC - C) • Pediatric Anxiety Rating Scale - Revised (PARS - R) • Clinical Global Impression — Severity and Improvement (n = 13 of 17 Period 1 Completers) March 2023

• Statistically significant improvements at 14 weeks and 38 weeks of treatment compared to baseline for multiple efficacy assessments: • The total score and all five subscales of the Anxiety, Depression and Mood Scale (ADAMS) • All five subscales of the Aberrant Behavior Checklist – Community (ABC - C) • Pediatric Anxiety Rating Scale - Revised (PARS – R) • The majority of patients showed clinically meaningful improvements at week 14 as demonstrated by the Clinical Global Impression – Improvement (CGI - I) • Seventy - five percent of patients were rated by the clinicians as “improved”, “much improved” or “very much improved” • Nearly two - thirds (62.5%) of the patients being “much improved” or “very much improved” • Zygel was shown to be well tolerated over 38 weeks, and the safety profile was consistent with previously reported data from other Zygel clinical trials • Three patients reported treatment related adverse events which were all mild application site adverse events • Three patients experienced a serious adverse event unrelated to Zygel • One patient discontinued treatment due to adverse events not related to Zygel 28 Positive Topline Results from INSPIRE Trial Zynerba Pharmaceuticals | Advancing Science. Improving Connections. March 2023

29 Efficacy: Significant Improvement in Anxiety as Measured by the PARS - R 14.7 8.5 0 2 4 6 8 10 12 14 16 PARS - R score 40.6% ( P =.0005) Baseline (n=15) Week 14 (n=15) 15.3 7.4 0 2 4 6 8 10 12 14 16 PARS - R score 49.4% ( P =.0001) Baseline (n=11) Week 38 (n=11) The efficacy analysis for Period 1 included 15 patients for PARS - R (2 patients did not have valid assessments at Week 14). The efficacy analysis for Period 2 included 11 patients; One patient discontinued the trial prior to week 38 and one patient who completed Week 38 stopped drug prior to completion. Improvement Improvement • The PARS - R is a clinical interview that assesses symptoms of anxiety and generates a composite score for: • Overall frequency of anxiety symptoms • Overall severity of anxiety feelings • Overall avoidance of anxiety - provoking situations • Interference with family relationships and/or performance at home • Interference with peer and adult relationships and/or performance outside of home • At Baseline, patients had clinically significant moderate anxiety on average (PARS - R=15) • At Weeks 14 and 38, patients had improved to minimal to mild anxiety on average (PARS - R=5 - 10) Period 1 14 weeks Period 2 38 weeks Mean Scores and Percentage Improvement March 2023

30 Efficacy: Significant Improvements in ADAMS Total and Subscale Scores Mean Scores and Percentage Improvement Period 1 14 weeks 36.1 10.4 7.6 8.7 3.0 7.6 17.7 5.1 3.4 4.3 1.1 4.4 0 5 10 15 20 25 30 35 40 Baseline (n=16) Week 14 (n=16) ADAMS total and subscale scores 45.3% ( P =.0005) 43.6% ( P= .0005) 50.3% ( P= .0033) 64.0% ( P= .0037) 41.3% ( P= .0084) 38.2% ( P= .0032) Improvement Total Score General Anxiety Depressed Mood Social Avoidance Obsessive - Compulsive Behavior Manic/ Hyperactive Behavior 36.1 11.5 7.8 9.6 2.8 7.6 15.9 4.7 2.8 4.5 0.7 3.8 0 5 10 15 20 25 30 35 40 Baseline (n=11) Week 38 (n=11) Obsessive - Compulsive Behavior Manic/ Hyperactive Behavior 56.6% ( P =.0064) 55.1% ( P= .0009) 64.5% ( P= .0219) 81.4% ( P= .0124) 33.5% ( P= .0191) 54.4% ( P= .0061) ADAMS total and subscale scores Total Score General Anxiety Depressed Mood Social Avoidance Period 2 38 weeks Improvement The efficacy analysis for Period 2 included 11 patients; One patient discontinued the trial prior to week 38 and one patient who completed Week 38 stopped drug prior to completion. Total Score and Obsessive/Compulsive Behavior N=10 as the score for one item was missing at Week 38 The efficacy analysis for Period 1 included 16 patients for ADAMS (1 patient did not have a valid assessment at Week 14). March 2023

31 Efficacy: Significant Improvements in All ABC - C Subscale Scores 18.4 4.2 3.9 14.4 18.1 10.0 2.4 1.6 7.9 10.4 0 2 4 6 8 10 12 14 16 18 20 Baseline (n=16) Week 14 (n=16) ABC - C subscale score 36.3% ( P =.0055) 18.3% ( P= .0166) 52.1% ( P= .0155) 16.5% ( P= .0091) 27.6% ( P= .011) Irritability Inappropriate Speech Stereotypy Social Withdrawal Hyperactivity 18.6 4.2 4.3 15.5 18.5 8.5 1.2 1.2 6.8 10.2 0 2 4 6 8 10 12 14 16 18 20 Baseline (n=11) Week 38 (n=11) 41.6% ( P =.0087) 63.3% ( P= .0028) 73.3% ( P= .0270) 48.1% ( P= .0232) 59.4% ( P= .0174) ABC - C subscale score Irritability Inappropriate Speech Stereotypy Social Withdrawal Hyperactivity Period 1 14 weeks Period 2 38 weeks Improvement Improvement Mean Scores and Percentage Improvement The efficacy analysis for Period 2 included 11 patients. One patient discontinued the trial prior to week 38 and one patient who completed Week 38 stopped drug prior to completion The efficacy analysis for Period 1 included 16 patients for ABC - C (1 patient did not have a valid assessment at Week 14). March 2023

Next Steps in 22q Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 32 Ongoing discussions with FDA regarding regulatory pathway (initial meeting Q4 2022) Finalize trial design with FDA in 2023; Initiate Phase 3 program after RECONNECT topline results March 2023

Positioned for Success

Leadership Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 34 Armando Anido Chairman of the Board and CEO Terri B. Sebree President Jim Fickenscher CFO and VP, Corporate Development Paul Kirsch VP, Regulatory Affairs and Quality Assurance Joe Apostolico VP, Human Resources Terry Hurst GM, Zynerba Pharmaceuticals Pty Ltd (Australia) Stephen O’Quinn, PharmD VP, Medical Affairs Albert P. Parker Chief Legal Officer Brian Rosenberger VP, Commercial and Business Development Nancy Tich, Ph.D. VP, Clinical Ray Mannion VP, Manufacturing Carol O’Neill VP, Development March 2023

Financial Strength Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 35 CASH AND CASH EQUIVALENTS $50.6M as of December 31, 2022; expected to be sufficient to fund operations and capital requirements to mid - year 2024 BALANCE SHEET CLEAN No debt, 53.4M shares outstanding (as of March 22, 2023) March 2023

A Year of Clinical Progress Ahead Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 36 Fragile X Syndrome (FXS) 22q Deletion Syndrome (22q) U.S. Orphan Drug and Fast Track designations; EU Orphan Drug designation U.S. and EU Orphan Drug designations Pivotal trial results expected in 1H 2024 Finalize regulatory pathway with FDA in 2023; Initiate Phase 3 after RECONNECT topline results March 2023

• Leader in transdermal cannabidiol delivery • Late - stage clinical company with two orphan CNS programs in areas of high unmet need • Launch Zygel in FXS via strategic partners in EU and other Territories • Launch Zygel into additional multi - billion $ market of 22q • Optimize Zygel growth with additional synergistic indications • Accelerate further growth through complimentary asset licensing and acquisition …and Beyond Zynerba Today… …in 2026 Zynerba Vision for Future Growth Zynerba Pharmaceuticals | Advancing Science. Improving Connections. 37 • Launch Zygel for FXS into a $1.9B+ U.S. market opportunity • Establish a fully integrated organization with U.S. commercial presence • Prepare for EU approval in FXS • Advance 22q Ph3 program towards completion March 2023

A different and exciting approach to Cannabidiol

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