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

45 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug Delta-8-THC compared to Delta-9-THC?

Research suggests that Delta-8-THC may help prevent vomiting in children undergoing cancer treatment, with minimal side effects. Additionally, Delta-8-THC is reported by users to be effective for anxiety, stress, depression, and chronic pain, with fewer negative effects compared to Delta-9-THC. ^{1 2 3 4 5}

Is Delta-8-THC safe for human use?

Delta-8-THC is similar to Delta-9-THC and may have fewer undesirable effects, but research is limited, and more studies are needed to confirm its safety. Some reports suggest it can cause sedation and other effects similar to Delta-9-THC, and there have been cases of severe reactions, especially in children. ^{2 3 6 7 8}

How does delta-8-THC differ from delta-9-THC as a drug?

Delta-8-THC is unique because it is generally legal under federal law, unlike delta-9-THC, and is reported to have similar effects with potentially fewer undesirable side effects. It is often used in forms like edibles and vaping concentrates, and while it shares many properties with delta-9-THC, it has a weaker affinity for the cannabinoid CB1 receptor, which may contribute to its reduced potency. ^{2 3 6 9 10}

What is the purpose of this trial?

Delta-8-THC is an isomer of delta-9-THC that has become widely available due to the legalization of hemp and its derivatives. Very little controlled research has been conducted with delta-8-THC and some research suggests it produces similar effects to delta-9-THC, albeit at lower potency. The present study will evaluate the dose effects of delta-8-THC, compared with delta-9-THC, on simulated driving performance, field sobriety tests, cognitive performance, and biomarkers of exposure to cannabinoids. The results will inform policy and education related to impairment due to acute delta-8-THC exposure via vaporization and oral ingestion.

Research Team

Ryan Vandrey, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

An efficient new cannabinoid antiemetic in pediatric oncology. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Marihuana-like activity of new synthetic tetrahydrocannabinols. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Sedation and Acute Encephalopathy in a Pediatric Patient Following Ingestion of Delta-8-Tetrahydrocannabinol Gummies. [2021]

9. England 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). [2023]

10. England pubmed.ncbi.nlm.nih.gov

Review of delta-8-tetrahydrocannabinol (Δ8 -THC): Comparative pharmacology with Δ9 -THC. [2022]