Delta-8-THC vs. Delta-9-THC for Cannabis Effects

Overseen By Tory Spindle, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive drugs

Disqualifiers: Health issues, Oral cavity disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: 0-8 hours per session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two forms of THC, delta-8 and delta-9, affect activities like driving and thinking. Researchers aim to determine if delta-8, which is less potent, has effects similar to the more common delta-9. Participants will consume or inhale different doses of these cannabinoids to assess their impact on performance and safety. Individuals who have used cannabis in the past three years and feel comfortable with its effects might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore these effects.

Will I have to stop taking my current medications?

The trial requires that you do not take any current medications that might interact with the study drugs, delta-8-THC and delta-9-THC.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that delta-9-THC, the main active ingredient in cannabis, can cause side effects like dizziness and dry mouth. However, it is usually well-tolerated when taken orally or inhaled. Approved by the FDA for certain uses, it has a known safety record.

In contrast, delta-8-THC has been studied less, and limited safety information is available. Some reports suggest it can cause intoxication and breathing issues, and poison control centers have received reports of negative effects. There isn't enough data to confirm its safety for use.

Both delta-8-THC and delta-9-THC can affect the mind, leading to euphoria, a strong sense of happiness. However, delta-8-THC seems to have milder effects. More research is needed to fully understand the safety of delta-8-THC, especially since it is less studied than delta-9-THC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Delta-8-THC and Delta-9-THC because they offer a new perspective on cannabis effects. Unlike most standard cannabis treatments that use Delta-9-THC as the main active ingredient, this trial explores the potential of Delta-8-THC, which is thought to produce milder psychoactive effects. Additionally, the study explores varying delivery methods, including oral consumption and vaporization, which could offer different onset times and potencies. This exploration could lead to more tailored and potentially safer cannabis therapies, expanding options for users seeking specific effects or therapeutic benefits.

What evidence suggests that this trial's treatments could be effective?

This trial will compare the effects of Delta-8-THC and Delta-9-THC. Research has shown that Delta-8-THC produces effects similar to Delta-9-THC but with less potency. Studies indicate that Delta-8-THC can alter mood and perception like Delta-9-THC, though with reduced intensity. Participants in this trial may receive Delta-9-THC, known for its long-lasting effects and its use in medicine to reduce chemotherapy-induced nausea. Both Delta-8-THC and Delta-9-THC can be vaporized to create feelings of euphoria or a "high," which is reportedly milder with Delta-8-THC. While more evidence exists for Delta-9-THC's effects, early research on Delta-8-THC suggests it functions similarly but may require higher doses to achieve the same effects. ^{2 6 7 8 9}

Who Is on the Research Team?

Ryan Vandrey, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals who can safely participate in simulated driving tests and are interested in understanding the effects of different THC compounds. Specific eligibility criteria details were not provided, so participants should inquire with the study organizers for more information.

Inclusion Criteria

Have a body mass index (BMI) in the range of 19 to 36 kg/m2

I am in good health as confirmed by recent medical exams and tests.

Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission

Exclusion Criteria

Participation in other research projects that could impact the present study

I am taking medications that might interact with the study drug.

History of or current evidence of health issues judged by the investigator to put the participant at greater risk of experiencing an adverse event due to drug exposure or completion of other study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral and inhaled doses of ∆8-THC and ∆9-THC, as well as placebo, to evaluate effects on simulated driving performance and cognitive tests

0-8 hours per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Delta-8-THC
• Delta-9-THC

Trial Overview

The study is testing how Delta-8-THC compares to Delta-9-THC and a placebo on simulated driving performance. It will also look at their effects on field sobriety tests, cognitive abilities, and cannabinoid levels in the body after vaporization or oral ingestion.

How Is the Trial Designed?

Group I: Oral administration of 60mg ∆8-THC Experimental Treatment 1 Intervention

A brownie infused with 60mg ∆8-THC will be eaten by study participants

Group II: Oral administration of 30mg ∆9-THC Experimental Treatment 1 Intervention

A brownie infused with 30mg ∆9-THC will be eaten by study participants

Group III: Oral administration of 30mg ∆8-THC Experimental Treatment 1 Intervention

A brownie infused with 30mg ∆8-THC will be eaten by study participants

Group IV: Administration of vaporized 60mg ∆8-THC Experimental Treatment 1 Intervention

Participants will inhale 60mg ∆8-THC using a handheld vaporizer (minimum 15 "puffs")

Group V: Administration of vaporized 30mg ∆9-THC Experimental Treatment 1 Intervention

Participants will inhale 30mg ∆9-THC using a handheld vaporizer (minimum 15 "puffs")

Group VI: Administration of vaporized 30mg ∆8-THC Experimental Treatment 1 Intervention

Participants will inhale 30mg ∆8-THC using a handheld vaporizer (minimum 15 "puffs")

Group VII: Oral Placebo Placebo Group 1 Intervention

A brownie containing no experimental drugs will be eaten by study participants

Group VIII: Administration of vaporized Placebo Placebo Group 1 Intervention

Participants will inhale ambient air through a handheld vaporizer (minimum 15 "puffs")

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Substance Abuse and Mental Health Services Administration (SAMHSA)

Collaborator

Trials

31

Recruited

23,300+

Published Research Related to This Trial

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has well-documented therapeutic benefits, including reducing nausea from chemotherapy, increasing appetite, alleviating pain, and relieving symptoms of multiple sclerosis, supported by extensive research over the past 30 years.

While Delta(9)-THC can impair cognitive functions such as memory and perception, and may induce negative psychological effects like panic and hallucinations, the long-term impacts are still unknown, leading to a proposal by WHO to reschedule it as a low-risk substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The good and the bad effects of (-) trans-delta-9-tetrahydrocannabinol (Delta 9-THC) on humans. Carlini, EA.[2013]

Newly synthesized cannabinoids, including 11-Methy-delta8- and 9-nor-delta8-THC, showed significant cannabinoid activity, producing effects like static ataxia and hypotension in dogs, and decreased activity in mice.

The study indicates that the 11-hydroxy metabolites of delta8- and delta9-THC are not the only contributors to THC's biological effects, as some synthetic analogs demonstrated varying levels of activity compared to traditional THC forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marihuana-like activity of new synthetic tetrahydrocannabinols. Martin, BR., Dewey, WL., Harris, LS., et al.[2019]

A survey of delta-8-THC consumers revealed that over half (51%) use it to treat various health conditions, with anxiety and stress being the most common, suggesting potential therapeutic benefits.

Participants reported favorably comparing delta-8-THC to delta-9-THC and pharmaceutical drugs, indicating it may have similar efficacy with potentially fewer adverse effects, although knowledge about safe dosages and medical integration remains low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumer Experiences with Delta-8-THC: Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC. Kruger, DJ., Kruger, JS.[2023]

In a study involving 10 experienced marijuana smokers, oral Delta-9-tetrahydrocannabinol (Delta(9)-THC) was found to be chosen more often than a placebo, indicating some reinforcing effects, although participants selected it less than 50% of the time.

Both doses of Delta(9)-THC (10 mg and 20 mg) led to significant increases in positive subjective effects, impaired psychomotor performance, and increased heart rate, suggesting potential safety concerns alongside its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Hart, CL., Haney, M., Vosburg, SK., et al.[2022]

The study found that the EMIT II Plus® Cannabinoid immunoassay can detect 11-nor-9-carboxy-Δ8-tetrahydrocannabinol (Δ8-THC-COOH) at concentrations of 30 ng/mL or higher, indicating that current testing methods may not adequately differentiate between Δ8-THC and Δ9-THC metabolites.

Gas chromatography-mass spectrometry (GC-MS) methods can effectively separate Δ8-THC-COOH from Δ9-THC-COOH, allowing for independent identification of these compounds, which is crucial for accurate drug testing and legal implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Delta-9-Tetrahydrocannabinol Carboxylic Acid (Δ9-THC-COOH) Immunoassay and a Gas Chromatography-Mass Spectrometry (GC-MS) Method for the Detection of Delta-8-Tetrahydrocannabinol Carboxylic Acid (Δ8-THC-COOH). Baird, SN., Frazee, CC., Garg, U.[2023]

Aerosolized delta9-tetrahydrocannabinol (THC) significantly increased airway conductance in healthy subjects, showing a maximum effect of 33-41% after 1-2 hours, although it was less effective than isoproterenol initially but surpassed it after 1-3 hours.

While aerosolized THC had minimal systemic side effects and showed some bronchodilation in asthmatic subjects, it also caused moderate to severe bronchoconstriction in some cases, indicating potential local irritation that may limit its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. Tashkin, DP., Reiss, S., Shapiro, BJ., et al.[2013]

Delta-8-tetrahydrocannabinol (Δ8-THC) has similar pharmacokinetics and pharmacodynamics to its more well-known isomer, delta-9-tetrahydrocannabinol (Δ9-THC), but is a partial agonist of the cannabinoid CB1 receptor, leading to reduced potency in clinical effects compared to Δ9-THC.

The review highlights the need for more research on Δ8-THC, especially in human studies, to better understand its pharmacological properties and potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of delta-8-tetrahydrocannabinol (Δ8 -THC): Comparative pharmacology with Δ9 -THC. Tagen, M., Klumpers, LE.[2022]

Delta-9-tetrahydrocannabinol (Delta(9)-THC) significantly reduces the viability of glioblastoma multiforme (GBM) cells by inducing G(0/1) cell cycle arrest, rather than causing apoptosis, as shown in experiments with human GBM cell lines U251-MG and U87-MG.

The mechanism of action involves the downregulation of E2F1 and Cyclin A proteins, which are crucial for cell cycle progression, while increasing the levels of the cell cycle inhibitor p16(INK4A), suggesting that Delta(9)-THC could be a promising therapeutic option for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. Galanti, G., Fisher, T., Kventsel, I., et al.[2013]

A case report of a 2-year-old girl who ingested delta-8 THC gummies showed severe symptoms, including encephalopathy, highlighting the potential dangers of delta-8 THC exposure in children.

Delta-8 THC products are increasingly available in the market, and their effects are similar to those of delta-9 THC, complicating diagnosis and treatment; however, symptomatic care is effective for managing cannabinoid toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sedation and Acute Encephalopathy in a Pediatric Patient Following Ingestion of Delta-8-Tetrahydrocannabinol Gummies. Akpunonu, P., Baum, RA., Reckers, A., et al.[2021]

Delta-8-tetrahydrocannabinol (delta-8-THC) was administered to eight children with hematologic cancers, and it successfully prevented vomiting associated with their antineoplastic treatments, demonstrating its efficacy in managing chemotherapy-induced nausea.

The treatment was well-tolerated, with negligible side effects reported over a total of 480 treatments, indicating a favorable safety profile for delta-8-THC in this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An efficient new cannabinoid antiemetic in pediatric oncology. Abrahamov, A., Abrahamov, A., Mechoulam, R.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9894081/

Delta-8, a Cannabis-Derived Tetrahydrocannabinol Isomer

An increase in D8-THC use led to a notable increase in cases of intoxication and nonfatal overdose to poison control centers and emergency room ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40288059/

A within-subject cross-over trial comparing the acute effects ...

Δ8-THC demonstrated dose-dependent psychoactive effects qualitatively similar to Δ9-THC but with reduced potency.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S030646032200140X

Delta-8 THC use in US adults: Sociodemographic ...

Among past 30-day cannabis users, 16.7% reported Delta-8 THC use. The most common consumption method was vaping concentrated formulations of Delta-8 THC (41.2%) ...

4.

bpspubs.onlinelibrary.wiley.com

bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15865

Review of delta-8-tetrahydrocannabinol (Δ 8 -THC ...

Δ8-THC is clearly less potent in humans relative to Δ9-THC, regardless of route of administration. Both intravenous and smoked routes, where a ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05287256

NCT05287256 | Comparative Pharmacokinetic and ...

This study compares the effects of inhaled and orally ingested Delta-8 THC to placebo and Delta-9 THC, using a crossover design with sub-studies.

6.

cdn.caymanchem.com

cdn.caymanchem.com/cdn/msds/14042m.pdf

Δ8-THC

Flammable liquids 2 H225 Highly flammable liquid and vapor. Acute toxicity - oral 3 H301 Toxic if swallowed.

7.

fda.gov

fda.gov/media/169551/download

delta(8) tetrahydrocannabinol (12/2/2021)

The available data on delta(8) THC are insufficient to support its safety for use as a food ingredient that will be consumed by the general ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8664123/

Δ8-THC: Legal Status, Widespread Availability, and Safety ...

Delta-8-tetrahydrocannabinol (Δ8-THC) is chemically and functionally similar to delta-9-tetrahydrocannabinol (Δ9-THC) (the primary psychoactive cannabinoid in ...

9.

opss.org

opss.org/article/delta-8-thc-prohibited-psychoactive-substance

Delta-8-THC: A prohibited psychoactive substance

Use of Delta-8-THC is prohibited by DoD, can result in a positive military drug test, and violate UCMJ. Delta-8-THC cannabis products are ...